CN108351303A - Hollow polymer fibre system for single analyte and multiplexing analysis analyte detection - Google Patents
Hollow polymer fibre system for single analyte and multiplexing analysis analyte detection Download PDFInfo
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- CN108351303A CN108351303A CN201680066530.3A CN201680066530A CN108351303A CN 108351303 A CN108351303 A CN 108351303A CN 201680066530 A CN201680066530 A CN 201680066530A CN 108351303 A CN108351303 A CN 108351303A
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Classifications
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N2021/6439—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks
- G01N2021/6441—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" with indicators, stains, dyes, tags, labels, marks with two or more labels
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
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- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
- G01N2021/7706—Reagent provision
- G01N2021/773—Porous polymer jacket; Polymer matrix with indicator
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7786—Fluorescence
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- G—PHYSICS
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- G01N2201/00—Features of devices classified in G01N21/00
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
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- G01N33/552—Glass or silica
Abstract
It is provided herein and is based on amplification Luminescent Proximity Homogenous analysis (" alpha ") technology, but the signal generated by singlet oxygen channel by the dopant using the hollow polymer optical fiber carrying doped with ' acceptor bead ' dyestuff (such as oxathiene, anthracene, rubrene and/or lanthanide series chelating agent) or ' donor bead ' dyestuff (such as phthalocyanine) analyzes method, system and the equipment of analyte detection to carry out single analysis analyte detection or multiplexing.In one embodiment, hollow polymer optical fiber (106) is doped with ' acceptor bead ' dyestuff.It is bound to the first of analyte of interest (110) inner surface for combining collocation object (108) to be bound to the optical fiber.The analyte may be contained and the sample solution of bead (114) is introduced into the inside of the optical fiber, the bead is embedded with ' donor bead ' dyestuff and is fixed on the surface thereof also in conjunction with the second combination collocation object (112) to the analyte.The analyte is bound to the donor bead and the optical fiber, thus makes neighbouring described ' acceptor bead ' dyestuff of described ' donor bead ' dyestuff.When being irradiated with exciting light (102), singlet oxygen is generated in ' donor bead ' dyestuff and is delivered to described ' acceptor bead ' dyestuff with channel, in ' acceptor bead ' dyestuff, it finally causes fluorescence (104) to emit, and the intensity of the fluorescence changes with the concentration of the analyte.
Description
Related application
The disclosure requires to submit on November 23rd, 2015 entitled " for single analyte and multiplexing analysis analyte detection
Hollow polymer fibre system (Hollow Polymer Fiber Optic System for Single Analyte and
Multiplexed Analyte Detection) " US provisional patent 62/259,000 priority, content with full text
The mode of reference is incorporated herein.
Technical field
The method, system and equipment for analyzing analyte detection is provided herein.For example, there is described herein use
The signal that doped hollow polymer optical fiber carrying is generated by dopant by singlet oxygen channel is to detect one in sample
Or method, system and the equipment of multiple analytes.
Background technology
It can be used for micro disk-form postgraduate object interaction of molecules there are many analytical technology based on bead, such as by
PerkinElmer (PerkinElmer) manufacture of Massachusetts Waltham (Waltham, MA)WithAcronym " Alpha " indicates that amplification Luminescent Proximity Homogenous analyzes (amplified luminescent
proximity homogeneous assay).These technologies are non-radioactive adjoining analyses.In conjunction with being trapped in pearl
Molecule on grain causes energy to be transferred to another bead from a bead, finally generates the detectable/fluorescence signal that shines, by
This provides the qualitative and quantitative information in relation to one or more analytes in sample.
WithIt is utilized respectively two kinds of bead types：Donor bead and acceptor bead
Grain.Ambient oxygen is converted to the active oxygen being stimulated by donor bead comprising photosensitizer, such as phthalocyanine when being irradiated at 680nm
Form, i.e. singlet oxygen.Singlet oxygen is not a kind of free radical；It is the molecular oxygen with the single electronics that is stimulated.With it is other
The molecule being stimulated is identical, and singlet oxygen is back to having the limited service life before ground state.It is compared to maximum transfer distance
The TR-FRET of about 10nm, singlet oxygen can spread about 200nm in the solution within the half-life period of its 4 microsecond.If acceptor bead
Grain is in this degree of approach, then energy is transferred to the oxathiene (thioxene) in acceptor bead from singlet oxygen, then
Cause to generate in a wavelength range, such as 520-620nmInterior or specific wavelength, such as 615nmLight.In the presence of no acceptor bead, singlet oxygen returns to ground state and does not generate signal.It is this close
Degree dependence chemical energy transfer is the basis of the homogeneous properties of AlphaScreen so that is different from elisa assay, electrochemistry is sent out
Light and flow cytometry do not need washing step, thus provide significant advantage.
WithDependent on identical donor bead, but use different acceptor beads.There are three types of dyestuffs for acceptor bead embedding：Oxathiene, anthracene and rubrene.Rubrene, i.e., final is glimmering
Photo etching emits the detectable light between 520-620nm.In acceptor bead, anthracene and rubrene are by europium
Chelating agent substitutes.Europium (Eu) chelating agent is reacted with singlet oxygen and be converted to caused by derovatives by oxathiene
340nm light directly excites.The europium chelating agent being excited is generated can examine in substantially narrower wavelength bandwidth centered on by about 615nm
The strong light surveyed.Therefore, withIt compares,Transmitting is less easily by absorption between 500-600nm
Light artificial or native compound (such as hemoglobin) interference.
WithTypically shape is analyzed with porous (such as 96 holes, 384 holes or 1536 holes)
Formula operates, and for carrying out biochemistry and the analysis based on cell.It can be used for down to high-affinity combination phase interaction
With (such as pM to mM), and it can be used for high flux screening (HTS).It is produced with complex matrices such as cell dissolution
Object, serum, blood plasma, CSF etc. are compatible.These systems can carry out immunoassay, epigenetic analysis, kinase assays, antibody inspection
It surveys and characterization, immunogenicity, selective enumeration method sAPP and 4 amyloid, α proteasome assays, alpha ligands-receptor assay, cAMP divides
Analysis, cGMP analyses and the detection of protein-protein and protein-nucleic acid interaction.
The AlphaPlex manufactured by the PerkinElmer of Massachusetts WalthamTMIt is using as described above
The homogeneous multiplexing reagent technique of one of alpha technologies.By using multiple acceptor beads of transmitting different wave length, Ke Yijian
Survey multiple analytes.The system provide to from larger protein to little albumen matter and rare biological sample such as primary cell and
The accurate multiplexing of the multiple analytes such as stem cell is quantitative, and is suitable for numerous applications, includes the biomarker of PD/PK
Object, the biomarker of stem cell, kinases (such as gross protein comparison phosphorylating protein), epigenetic marker (such as
Total histone compares particular marker), 4 amyloid, IgG spectrum analysis and the analysis that is carried out with house keeping protein matter it is regular.
Existing system using alpha technologies is not pocket.Crop science and animal health researcher/technician
It needs to obtain sample in the wild, these samples is then taken back into laboratory and are analyzed.Divided sample is taken back laboratory
When analysis, it may be necessary to obtain many samples to ensure that specific analyte of interest can be present at least part of these samples
In.
It includes lateral flow devices that pocket amino, which analyzes (aminoassay) device, such as the amino executed in medicine box point
Analysis, such as pregnancy tests, wherein sample and antibody response and while there is analyte in the sample, generate apparent color.Other pockets
System is related to measuring stick, such as is embedded with the paper or plastics of reagent, and measuring stick is immersed in solution to determine analyte in sample
Presence.These systems are usually less accurate, and are often limited to qualitative analysis.
Need it is more more acurrate than existing pocket system and it is more sensitive stablize, wieldy pocket analysis system and
Device.
Invention content
Be provided herein the above mentioned alpha technologies that are based on, but using doped with ' acceptor bead ' dyestuff and/or
The hollow polymer optical fiber of ' donor bead ' dyestuff carries out the method for single analysis analyte detection or multiplexing analysis analyte detection, is
System and equipment.For example, acceptor bead dyestuff can include oxathiene, anthracene, rubrene and/or lanthanide series chelating
Agent, such as europium chelating agent, terbium chelating agent, dysprosium chelating agent, samarium chelating agent, ytterbium chelating agent, erbium chelating agent and/or thulium chelating agent, and/
Or its version.' donor bead ' dyestuff can include that such as phthalocyanine, naphthalene phthalocyanine, chlorin, porphines, porphyrin, lacquer tree are blue
Albumen, chlorophyll, Bengal rose red and/or its version.Polymer optical fiber carrying is led to by dopant by singlet oxygen
The signal that road generates, the signal are detected and used to differentiate of interest a kind of analyte or multiple analytes in given sample
Presence and/or amount.
In certain embodiments, the system be pocket, it is wieldy, and provide to one or more of interest point
Analyse the stably measured (qualitative and/or quantitative) of object.Exactly, it for crop science and animal health application, traditionally needs
Sample is obtained in the wild and takes back laboratory is analyzed.Hollow polymer fibre system described herein provide for
The stabilization of such measurement, wieldy reliable system are carried out in field rather than laboratory.In addition, in view of in hollow optical fiber pipe
Portion's small volume, the sample of minimum volume with regard to being tested enough.Hollow tube also simplifies the acquisition, processing and transport of sample.
For example, sample can be obtained in the wild and these samples of external pelivimetry out of office are to detect depositing for one or more analytes
And/or amount (such as concentration).Also can external pelivimetry sample out of office to differentiate the presence of analyte of interest, then, if necessary
Further analysis, then only transport the sample containing analyte of interest back laboratory and further tested, rather than obtains simultaneously
Transport may largely contain or may be free of the sample of analyte of interest.For example, can use in the wild has excitation
Required sample can then be taken back laboratory and carry out more accurate measure by the pocket handheld apparatus of light source and detector.
When, there are when respective analyte, having by using different receptors and/or compound donator generation can in sample
The light of the different wave length of difference, it is possible to carry out multiplexing sample analysis.
For example, including being realized doped with the fiber optic bundle of multiple hollow polymer optical fiber of different acceptor dye compositions
The multiplexing of multiple analytes is detected.Different optical fiber in fiber optic bundle are taken by being coupled to different combine of its inner surface
The different analytes in the presence of the sample solution being introduced into optical fiber are captured with object (such as antibody).Doped with donor dye group
The donor bead for closing object is coated with and corresponding in conjunction with collocation object and is introduced into optical fiber (such as together with sample, such as by sample
In after product are introduced into optical fiber, in the second step), and it is bound to the respective analyte in optical fiber.When being irradiated with exciting light,
Donor dye in donor bead is excited so that from the fibre optical transmission light of doping acceptor dye.Doped with different acceptor dyes
The different optical fiber of composition generate diacritic different wave length (such as 545nm, such as 575nm, such as 615nm, such as 645nm)
Transmitting light.
In certain embodiments, the system includes that multiple detectors and optical filter combine, these combinations are diacritically examined
The transmitting light of different specific wavelengths is surveyed, these wavelength respectively correspond to the particular fiber in fiber optic bundle, and therefore correspond to by institute
State the specific analyte of optical fiber capture.
By using doped with different donor dye compositions different types of donor bead and doped with difference by
Multiple optical fiber of body dye composite, the multiplexing capacity that can further increase the system (can be used for example single
The quantity for the different analytes that optical fiber and/or fiber optic bundle diacritically detect).Exactly, in certain embodiments, the system
System irradiation optical fiber and/or fiber optic bundle under a variety of excitation wavelengths (such as 680nm, such as 775nm), thus depend on donor bead
The excitation wavelength of the donor dye composition adulterated, the different types of donor bead of selective excitation.In response to particular excitation
It is possible thereby to associated with certain types of donor bead, the donor bead is coated with knot for wavelength illumination and the transmitting light that generates
It is bonded to the particular combination collocation object of specific analyte.
Therefore, each analyte in multiple analytes can by means of and be bound to analyte combination collocation object coupling
Donor bead and particular fiber (such as doped with special receptor dyestuff) type and with excitation and launch wavelength specific group
It closes associated.The method can also be carried out by reversing the effect of bead and optical fiber, wherein different types of acceptor bead is adulterated
There are different acceptor dye compositions, without same optical fiber doped with different donor dye compositions.Therefore, system as described herein
The a variety of flexible and effective method for the multiplexing detection of multiple analytes in sample is provided with method.
In addition, in certain embodiments, the fiber optic bundle that the multiplexing for carrying out analyte detects, which is disposed in, includes
In the chuck (cartridge) of multiple fiber optic bundles.In certain embodiments, multiple samples are detected using multiple fiber optic bundles in chuck
Multiple analytes in product, the multiple fiber optic bundle respectively by means of different doping described above and can combine collocation object to match
Set detection multiple analytes.For example, in given chuck, each fiber optic bundle can be contacted with different samples, be achieved in
Analyte detection is analyzed in multiplexing in multiple samples.
In certain embodiments, in chuck the arrangement of fiber optic bundle can be used for simplify for multiplex detection doping with
In conjunction with collocation object configuration.For example, each fiber optic bundle in chuck can be used to detect different analytes.Make in a chuck
Multiple fiber optic bundles contacted with the sample solution comprising sample to be analysed, and by irradiating each fiber optic bundle with exciting light and examining
It surveys and thus obtained emits light to read these fiber optic bundles.Multiple fiber optic bundles in one chuck can be read sequentially or parallel.
Therefore, in certain embodiments, detect different respective analytes using each fiber optic bundle in chuck and diacritically detect
Signal (such as by sequentially reading the signal from each fiber optic bundle) from each fiber optic bundle, avoids in fiber optic bundle
The demand of complicated receptor and/or donor dye the doping configuration of different optical fiber, thereby simplifies detection process.
Therefore, fiber optic bundle chuck provide for for example detect in the wild the simple of the multiple analytes in multiple samples and
Convenient method.
The aliquot of sample can suck one or more hollow optical fibers (such as miniature fiber beam) by capillarity
In.Smaller required sample size, low cost, the accuracy that is easy to transport, portability, adaptive and measurement make the method phase
There is the advantage of synergy for traditional micro disk-form and existing lateral flow devices and measuring stick.
In one aspect, the present invention relates to a kind of doped with the poly- of acceptor dye composition and/or donor dye composition
Object light fibre is closed, the optical fiber can transmit the light generated by singlet oxygen channel to detect and/or quantify being closed in sample
Note analyte.
In certain embodiments, polymer optical fiber is doped with acceptor dye composition.In certain embodiments, acceptor dye
Composition includes chemiluminescence singlet oxygen receptor and fluorescent chemicals.In certain embodiments, chemiluminescence singlet oxygen by
Body is selected from the group being made up of：Oxathiene, dioxine and dithia cyclohexene.In certain embodiments,
Fluorescent chemicals are lanthanide series chelating agents.In certain embodiments, lanthanide series chelating agent includes to be selected from group consisting of
Lanthanide series：Europium, terbium, dysprosium, samarium, ytterbium, erbium and thulium.In certain embodiments, fluorescent chemicals include organic dyestuff (such as
Anthracene, rubrene).In certain embodiments, polymer optical fiber is doped with quantum dot.
In certain embodiments, polymer optical fiber is doped with donor dye composition.In certain embodiments, donor dye
Composition includes the photosensitizer that singlet oxygen is discharged when being irradiated with exciting light.In certain embodiments, photosensitizer be selected from
The compound of the group of lower composition：Phthalocyanine, naphthalene phthalocyanine, chlorin, porphines, porphyrin, stellacyanin, chlorophyll and Bangladesh's rose
It is rare red.
In certain embodiments, the outer diameter of internal diameter and 1mm to 3mm of the polymer optical fiber with 0.1mm to 2mm.Certain
In embodiment, the internal diameter of polymer optical fiber is 0.5mm to 1.5mm.In certain embodiments, the internal diameter of polymer optical fiber is sufficiently small
To be drawn liquid into the inside of polymer optical fiber by capillarity.In certain embodiments, the internal diameter of polymer optical fiber
Capillarity is kept so that liquid (such as wrapping solution with sample) is sucked by capillarity in polymer optical fiber
(led to by singlet oxygen for example, the distance that wherein liquid is sucked by capillarity in optical fiber is at least enough to detect in portion
The distance (for example, at least one millimeter) for the transmitted light that road generates).
In certain embodiments, polymer optical fiber includes that first be incorporated on the inner surface of polymer optical fiber combines collocation
Object (such as first antibody, such as streptavidin).In certain embodiments, polymer optical fiber includes multiple along its length
Discontinuous part, the part first combine collocation object to be coupled to its inner surface to realize to the respectively with various concentration
The measurement of a variety of level of sensitivity for the analyte of interest that one combination collocation object is combined.In certain embodiments, polymer
Optical fiber includes multiple discontinuous parts along its length, and respectively there is different combination collocation objects to be coupled to its interior table for these parts
Face.In certain embodiments, different combinations collocation object is different antibody.In certain embodiments, each combination collocation object
The different variants of specific antigen can be bound to.In certain embodiments, each combination collocation object can be bound to different analyses
Object.
In certain embodiments, polymer optical fiber include multiple hollow cores (such as polymer optical fiber include 5 to 20 it is hollow
Core).
In certain embodiments, polymer optical fiber includes polystyrene and/or poly- (methyl methacrylate).
On the other hand, the present invention relates to polymer optical fiber beams, and each optical fiber of fiber optic bundle is doped with corresponding acceptor dye group
Close object and/or donor dye composition.In certain embodiments, fiber optic bundle includes 2 to 20 polymer optical fibers.
In certain embodiments, multiple polymer optical fibers of fiber optic bundle are respectively doped with unique acceptor dye composition.
In certain embodiments, acceptor dye composition includes chemiluminescence singlet oxygen receptor and fluorescent chemicals.In certain implementations
In example, chemiluminescence singlet oxygen receptor is selected from the group being made up of：Oxathiene, dioxine and dithia
Cyclohexene.In certain embodiments, fluorescent chemicals are lanthanide series chelating agents.In certain embodiments, lanthanide series chelates
Agent includes the lanthanide series selected from group consisting of：Europium, terbium, dysprosium, samarium, ytterbium, erbium and thulium.In certain embodiments, Fluoresceinated
It includes organic dyestuff (such as anthracene, rubrene) to close object.In certain embodiments, one or more polymer optical fibers are doped with quantum
Point.
In certain embodiments, multiple polymer optical fibers of fiber optic bundle are respectively doped with unique donor dye composition.
In certain embodiments, donor dye composition includes the photosensitizer that singlet oxygen is discharged when being irradiated with exciting light.Certain
In embodiment, photosensitizer is the compound selected from group consisting of：Phthalocyanine, naphthalene phthalocyanine, chlorin, porphines, porphyrin, lacquer tree
Azurin, chlorophyll and Bengal rose red.
In certain embodiments, respectively there is multiple polymer optical fibers of fiber optic bundle unique combination collocation object to be coupled to it
Inner surface.
On the other hand, the present invention relates to the chucks for including multiple polymer optical fiber beams, wherein each of each fiber optic bundle is poly-
Object light fibre is closed doped with corresponding acceptor dye composition and/or corresponding donor dye composition.In certain embodiments, receptor contaminates
Feed composition includes chemiluminescence singlet oxygen receptor and fluorescent chemicals.In certain embodiments, chemiluminescence singlet oxygen
Receptor is selected from the group being made up of：Oxathiene, dioxine and dithia cyclohexene.In some embodiments
In, fluorescent chemicals are lanthanide series chelating agents.In certain embodiments, lanthanide series chelating agent includes selected from consisting of
The lanthanide series of group：Europium, terbium, dysprosium, samarium, ytterbium, erbium and thulium.In certain embodiments, fluorescent chemicals include organic dyestuff (such as
Anthracene, rubrene).In certain embodiments, one or more polymer optical fibers are doped with quantum dot.
In certain embodiments, for each fiber optic bundle in chuck, multiple polymer optical fibers of fiber optic bundle respectively have
Unique combination collocation object is coupled to its inner surface.
On the other hand, the present invention relates to a kind of system for carrying out single analyte and/or multiple analytes detection, institutes
The system of stating includes：Doped with acceptor dye composition and/or the polymer optical fiber of donor dye composition；Excitation light source；And
Detector for detecting the transmitting light generated by singlet oxygen channel for travelling across polymer optical fiber.
In certain embodiments, the detector passes through alignment to detect the light for the end face for leaving the polymer optical fiber.
In certain embodiments, the detector process is aligned so that its zone of action and the axis of polymer optical fiber is substantially concentric.
In certain embodiments, excitation light source passes through alignment to irradiate polymer optical fiber along the length of polymer optical fiber.In certain implementations
In example, excitation light source is by alignment to irradiate polymer optical fiber on the direction perpendicular to polymer optical fiber.In some embodiments
In, excitation light source is with the laser of substantially unitary wavelength operation.
In certain embodiments, the system also includes shell, wherein：The shell surrounds detector and polymer light
Fibre, the shell include excitation optical port, can the exciting light of self-excitation in future light emitting source be directed across the excitation optical port, and
And the shell is substantially opaque to ambient light.
In certain embodiments, the system also includes shell, wherein：The shell surrounds detector, polymer optical fiber
And excitation light source, and the shell is substantially opaque to ambient light.
In certain embodiments, the system includes self contained pocket power supply, for being supplied to detector and excitation light source
It is pocket thus without external power supply and the system to electric power.In certain embodiments, the power supply includes electricity
Pond.
In certain embodiments, the system is comprised in shell, and the shell is defined no more than 750cm3Volume
(such as the size of the system is no more than 150mm × 100mm × 50mm, such as and/or the weight of the system be no more than
2lbs., such as weight are 1 to 2lbs.).In certain embodiments, the shell is defined no more than 750cm3Volume (such as
The size of the system be no more than 150mm × 100mm × 50mm, such as and/or the system weight be no more than 2lbs., example
If weight is 1 to 2lbs.).In certain embodiments, the total weight of the system is no more than 2lbs. (such as the system is total
Weight is 1 to 2lbs.).
In certain embodiments, polymer optical fiber is doped with acceptor dye composition, and excitation light source it is operable with
Polymer is irradiated under the excitation wavelength for the donor dye composition that donor particle in polymer optical fiber inside to be introduced is included
Optical fiber.
In certain embodiments, the launch wavelength for the acceptor dye composition that the detector adulterates polymer optical fiber
Light react.
In certain embodiments, the system includes the optical filter being positioned between polymer optical fiber and detector, wherein
The optical filter wavelength is corresponded to the excitation wavelength of donor dye composition light is substantially opaque and the optical filter
Substantially transmission peak wavelength corresponds to the light of the launch wavelength for the acceptor dye composition that polymer optical fiber is adulterated.
In certain embodiments, polymer optical fiber is doped with donor dye composition, and excitation light source it is operable with
Polymer optical fiber is irradiated under the excitation wavelength of donor dye composition.
In certain embodiments, the detector to the acceptor particles in polymer optical fiber inside to be introduced included by
The light of the launch wavelength of body dye composite reacts.
In certain embodiments, the system includes the optical filter being positioned between polymer optical fiber and detector, wherein
The optical filter corresponds to wavelength the light of the excitation wavelength for the donor dye composition that polymer optical fiber is adulterated substantially not
The transparent and described optical filter substantially transmission peak wavelength corresponds to the light of the launch wavelength of acceptor dye composition.
In certain embodiments, the system includes polymer optical fiber beam, each polymer optical fiber of fiber optic bundle doped with
Corresponding acceptor dye composition and/or donor dye composition.In certain embodiments, multiple polymer optical fibers of fiber optic bundle are each
It is coupled to its inner surface from different combinations collocation object (such as different antibodies).
In certain embodiments, the first polymer optical fiber of fiber optic bundle is doped with the first receptor with the first launch wavelength
Dye composite, the second polymer optical fiber of fiber optic bundle doped with the Co receptor dye composite with the second launch wavelength,
Second launch wavelength is different from first launch wavelength, and the first polymer optical fiber of fiber optic bundle has first to combine collocation
Object is coupled to its inner surface, and the second polymer optical fiber of fiber optic bundle has second object of arranging in pairs or groups is combined to be coupled to its inner surface,
Described second is different from described first in conjunction with collocation object combines collocation object.In certain embodiments, the system includes the first inspection
Device and the second detector are surveyed, first launch wavelength of the first detector pair reacts and second detector pair second is sent out
Ejected wave length reacts.In certain embodiments, the system includes (such as the changeable filter of the first optical filter and the second optical filter
Mating plate), wherein the first optical filter substantially transmits the first launch wavelength and substantially opaque to the second launch wavelength, and
Two optical filters substantially transmit the second launch wavelength and substantially opaque to the first launch wavelength.
In certain embodiments, the first polymer optical fiber of fiber optic bundle is doped with the first donor with the first excitation wavelength
Dye composite, the second polymer optical fiber of fiber optic bundle doped with the second donor dye composition with the second excitation wavelength,
Second excitation wavelength is different from first excitation wavelength, and the first polymer optical fiber of fiber optic bundle has first to combine collocation
Object is coupled to its inner surface, and the second polymer optical fiber of fiber optic bundle has second object of arranging in pairs or groups is combined to be coupled to its inner surface,
Described second is different from described first in conjunction with collocation object combines collocation object.In certain embodiments, the system includes first sharp
It rises and the second excitaton source, first excitaton source is operable with the irradiation optical fiber beam under the first excitation wavelength and described second
Excitaton source is operable with the irradiation optical fiber beam under the second launch wavelength.
In certain embodiments, the detector is focal plane arrays (FPA) (such as CCD, CMOS phase comprising multiple pixels
Machine), and emit the different pixels group that light irradiates the focal plane arrays (FPA) out of each polymer optical fiber of the polymer optical fiber beam.
On the other hand, the present invention relates to a kind of for detecting the signal from hollow core polymer optical fiber to carry out single point
The pocket system (such as hand held system) of object and/or multiple analytes detection is analysed, the system includes：Detector (such as
The detector that the launch wavelength of the acceptor dye composition adulterated to the polymer optical fiber for being intended to be inserted into the system reacts,
Such as the inspection that the launch wavelength of the acceptor dye composition adulterated to the acceptor particles in polymer optical fiber to be introduced reacts
Survey device)；For keep polymer optical fiber and/or polymer optical fiber beam and make its with the detector in line (such as so that
Optical fiber and/or fiber optic bundle keep straight enough, and make the axis pointing direction detectors oriented along optical fiber and/or fiber optic bundle) optical fiber pacify
It shelves；(such as wherein exciting light includes wave to excitaton source for irradiating polymer optical fiber and/or polymer optical fiber beam with exciting light
The light of the long excitation wavelength for corresponding to the donor dye composition that the polymer optical fiber for being intended to be inserted into the system is adulterated, such as
Wherein exciting light includes the donor dye combination that wavelength is included corresponding to the donor particle in polymer optical fiber inside to be introduced
The light of the excitation wavelength of object)；And shell, wherein：The shell surrounds detector, optical fiber mounting bracket and excitaton source, and institute
It is substantially opaque to ambient light to state shell.
In certain embodiments, the detector passes through alignment to detect the light for the end face for leaving the polymer optical fiber.
In certain embodiments, the detector process is aligned so that its zone of action and the axis of polymer optical fiber is substantially concentric.
In certain embodiments, excitation light source passes through alignment to irradiate polymer optical fiber along the length of polymer optical fiber.In certain implementations
In example, excitation light source is by alignment to irradiate polymer optical fiber on the direction perpendicular to polymer optical fiber.In some embodiments
In, excitation light source is with the laser of substantially unitary wavelength operation.
In certain embodiments, the shell is defined no more than 750cm3Volume (such as the size of the system does not surpass
Cross 150mm × 100mm × 50mm).In certain embodiments, the total weight of the system is no more than 2lbs. (such as systems
Total weight be 1 to 2lbs.).
In certain embodiments, detector reacts to the launch wavelength of acceptor dye composition, and thus detector detects
The transmitting light of acceptor particles from polymer optical fiber and/or doped with acceptor dye composition.In certain embodiments, described
System includes the optical filter being positioned in front of detector, wherein the optical filter is basic to the light of the wavelength with the exciting light
It is upper opaque, and the optical filter substantially transmission peak wavelength corresponds to the light of the launch wavelength of acceptor dye composition, thus
Make the filter transmission from polymer optical fiber and/or the transmitting light of acceptor particles doped with acceptor dye composition.
In certain embodiments, the system includes the first detector and the second detector, first detector pair the
One acceptor dye composition (such as the first acceptor dye combination that first polymer optical fiber and/or the first acceptor particles are adulterated
Object) the first launch wavelength react, and second detector is to Co receptor dye composite (such as second polymer
The Co receptor dye composite that optical fiber and/or Co receptor particle are adulterated) the second launch wavelength react, wherein described
Second launch wavelength is different from first launch wavelength.
In certain embodiments, the system includes (such as the changeable optical filtering of the first optical filter and the second optical filter
Piece), wherein first optical filter substantially transmits the first acceptor dye composition (such as first polymer optical fiber and/or
The first acceptor dye composition that one acceptor particles are adulterated) the first launch wavelength and to Co receptor dye composite
Second launch wavelength of (such as second polymer optical fiber and/or Co receptor particle are adulterated Co receptor dye composite)
It is substantially opaque, wherein second launch wavelength is different from first launch wavelength, and the second optical filtering chip base
Second launch wavelength and substantially opaque to first launch wavelength is transmitted on this.
In certain embodiments, the system includes the first excitaton source and the second excitaton source, and first excitaton source can be grasped
Make to generate the exciting light with the first excitation wavelength, first excitation corresponds to donor dye composition, and (such as first is poly-
Close the donor dye composition that object light is fine and/or the first donor particle is adulterated) excitation wavelength, and second excitaton source
The operable exciting light with generation with the second excitation wavelength, second excitation wavelength correspond to the second donor dye composition
The excitation wavelength of (such as first polymer optical fiber and/or the first donor particle are adulterated the second donor dye composition),
Described in the second excitation wavelength be different from first excitation wavelength.
On the other hand, the present invention relates to a kind of for detecting and/or quantifying one or more analyte of interest in sample
Method, the method include：Sample solution is introduced into the inside of polymer optical fiber, the solution includes that one or more are of interest
Analyte and donor particle, the donor particle include donor dye composition and particle combine collocation object (such as first antibody,
Such as streptavidin), wherein the polymer optical fiber, which includes acceptor dye composition and optical fiber, combines collocation object；It will swash
It shines and is conducted through the polymer optical fiber；And detection travels across the transmitting light of the polymer optical fiber, the transmitting light
It is to be generated by singlet oxygen channel, thus detects and/or quantify the analyte of interest in the sample.
In certain embodiments, the method includes that sample solution is introduced to multiple polymer optical fibers of polymer optical fiber beam
Inside in, wherein each polymer optical fiber is doped with corresponding acceptor dye composition and includes that corresponding optical fiber combines collocation object.
In certain embodiments, respectively there is multiple polymer optical fibers of fiber optic bundle different optical fiber to combine collocation object (example
Such as different antibodies) it is coupled to its inner surface (such as to allow to detect different analyte of interest).
In certain embodiments, the first polymer optical fiber of fiber optic bundle is doped with the first receptor with the first launch wavelength
Dye composite, the second polymer optical fiber of fiber optic bundle doped with the Co receptor dye composite with the second launch wavelength,
Second launch wavelength is different from first launch wavelength, and the first polymer optical fiber of fiber optic bundle is combined with the first optical fiber
Collocation object is coupled to its inner surface, and there is the second polymer optical fiber of fiber optic bundle the second optical fiber collocation object to be combined to be coupled to it
Inner surface, second optical fiber are different from first optical fiber in conjunction with collocation object and combine collocation object.
In certain embodiments, the method includes the light and wave that diacritically Detection wavelength corresponds to the first launch wavelength
The long light corresponding to the second launch wavelength.
In certain embodiments, the method includes：To include that donor dye composition and the first particle combine collocation object
The first donor particle be introduced into sample solution, wherein first particle combines collocation object to be bound to the first analyte, first
Optical fiber is in conjunction with collocation object also in relation with extremely first analyte；To include that donor dye composition and the second particle combine collocation object
The second donor particle be introduced into sample solution, wherein second particle combine collocation object be bound to (such as can be bound to/
It is designed to be bound to) the second analyte, the second optical fiber is in conjunction with collocation object also in relation with extremely second analyte；To include first
In the inside for the polymer optical fiber that the sample solution of donor particle and the second donor particle is introduced into polymer optical fiber beam.
In certain embodiments, the method includes：(a) will include that the first donor dye composition and the first particle combine
First donor particle of collocation object is introduced into sample solution, wherein first particle combines collocation object to be bound to the first analysis
Object；(b) the second donor particle of collocation object will be combined to introduce sample solution comprising the second donor dye composition and the second particle
In, wherein second particle combines collocation object to be bound to (such as can be bound to/be designed to and be bound to) second analyte；
(c) in the inside for the polymer optical fiber that the sample solution comprising the first donor particle and the second donor particle is introduced into fiber optic bundle,
Wherein：There is the first polymer optical fiber of fiber optic bundle the first optical fiber collocation object to be combined to be coupled to its inner surface, and the second of fiber optic bundle
There is polymer optical fiber the second optical fiber collocation object to be combined to be coupled to its inner surface, and described second is different from described the in conjunction with collocation object
One combines collocation object, and first optical fiber is bound to first analyte in conjunction with collocation object, and second optical fiber combines
Collocation object is bound to second analyte；(d) it is thus obtained with the exciting light irradiation optical fiber beam with first wave length and detection
Transmitting light, the first wave length correspond to the first donor dye composition excitation wavelength；And (e) with second wave length
Exciting light irradiation optical fiber beam and detect thus obtained transmitting light, the second wave length correspond to the second donor dye composition
Excitation wavelength.
On the other hand, the present invention relates to a kind of for detecting and/or quantifying one or more analyte of interest in sample
Method, the method include：Sample solution is introduced into the inside of polymer optical fiber, the solution includes that one or more are of interest
Analyte and acceptor particles, the acceptor particles include that acceptor dye composition and particle combine collocation object (such as first is anti-
Body), wherein the polymer optical fiber, which includes donor dye composition and optical fiber, combines collocation object (such as secondary antibody)；It will excitation
Light is conducted through the polymer optical fiber；And detection travels across the transmitting light of the polymer optical fiber, the transmitting is just
It is generated by singlet oxygen channel, thus detects and/or quantify the analyte of interest in the sample.
In certain embodiments, the method includes that sample solution is introduced to multiple polymer optical fibers of polymer optical fiber beam
Inside in, wherein each polymer optical fiber is doped with corresponding donor dye composition and includes that corresponding optical fiber combines collocation object.
In certain embodiments, multiple polymer optical fibers of polymer optical fiber beam respectively there is different optical fiber to combine collocation
Object (such as different antibodies) is coupled to its inner surface (such as to allow to detect different analyte of interest).
In certain embodiments, the method includes：To include that the first acceptor dye composition and the first particle are combined and taken
The first acceptor particles with object are introduced into sample solution, wherein the first acceptor dye composition has the first launch wavelength；
The Co receptor particle of collocation object will be combined to be introduced into sample solution comprising Co receptor dye composite and the second particle, wherein
The Co receptor dye composite has the second launch wavelength different from the first launch wavelength, and the second particle knot
It closes collocation object and is different from first particle combination collocation object；Sample comprising the first acceptor particles and Co receptor particle is molten
Liquid is introduced into the inside of the polymer optical fiber of fiber optic bundle, wherein：One or more polymer optical fibers of fiber optic bundle have the first optical fiber
It is coupled to inner surface in conjunction with collocation object, wherein first optical fiber combines collocation object to be bound to the first analyte, the first particle knot
Collocation object is closed also in relation with extremely first analyte, and one or more polymer optical fibers of fiber optic bundle are combined with the second optical fiber
Collocation object is coupled to inner surface, wherein second optical fiber combines collocation object to be bound to the second analyte, the second particle is combined and taken
With object also in relation with extremely second analyte.
In certain embodiments, the method includes the light and wave that diacritically Detection wavelength corresponds to the first launch wavelength
The long light corresponding to the second launch wavelength.
In certain embodiments, the method includes：(a) the first acceptor particles of collocation object will be combined comprising the first particle
It is introduced into sample solution, wherein first particle combines collocation object to be bound to the first analyte；(b) it will include the second particle knot
The Co receptor particle for closing collocation object is introduced into sample solution, wherein second particle combine object of arranging in pairs or groups to be bound to (such as can
Enough it is bound to/is designed to and is bound to) the second analyte；(c) by the sample comprising the first acceptor particles and Co receptor particle
Solution is introduced into the inside of the polymer optical fiber of fiber optic bundle, wherein：The first polymer optical fiber of fiber optic bundle is doped with the first donor
Dye composite and collocation object is combined to be coupled to its inner surface with the first optical fiber, the second polymer optical fiber doping of fiber optic bundle
There is the second donor dye composition and combine collocation object to be coupled to its inner surface with the second optical fiber, described second combines collocation
Object is different from described first and collocation object, first optical fiber is combined to be bound to first analyte in conjunction with collocation object, and described the
Two optical fiber are bound to second analyte in conjunction with collocation object；(d) with the exciting light irradiation optical fiber Shu Bingjian with first wave length
Thus obtained transmitting light is surveyed, the first wave length corresponds to the excitation wavelength of the first donor dye composition；And (e) apparatus
There is the exciting light irradiation optical fiber beam of second wave length and detect thus obtained transmitting light, the second wave length corresponds to the second donor
The excitation wavelength of dye composite.
In certain embodiments, sample solution is introduced into the inside of polymer optical fiber includes that polymer optical fiber is immersed sample
Sample solution is sucked in the inside of polymer optical fiber with will pass through capillarity in product solution.
In certain embodiments, particle combines collocation object to be at least bound to first point in one or more analyte of interest
Object and optical fiber are analysed in conjunction with collocation object also in relation with to first analyte.
In certain embodiments, polymer optical fiber includes along its length multiple discontinuous parts, and the part respectively has
There is the first or second of various concentration that collocation object is combined to be coupled to its inner surface to realize to a variety of sensitive of analyte of interest
Spend horizontal measurement.In certain embodiments, polymer optical fiber includes multiple discontinuous parts along its length, and the part is each
It is coupled to its inner surface from different combination collocation objects (such as different antibodies).
On the other hand, the present invention relates to a kind of kit, it includes：Polymer optical fiber as described in this article；And
One or more reagents of the sample for detecting one or more analyte of interest are used to prepare, one or more described reagents include
Acceptor particles (such as acceptor bead) and/or donor particle (such as donor bead).
On the other hand, the present invention relates to a kind of kit, it includes：Polymer optical fiber beam as described in this article；With
And one or more reagents of the sample for detecting one or more analyte of interest are used to prepare, one or more described reagent packets
Containing acceptor particles (such as acceptor bead) and/or donor particle (such as donor bead).
On the other hand, the present invention relates to a kind of kit, it includes：Chuck as described in this article；And for making
Available detects one or more reagents of the sample of one or more analyte of interest, one or more described reagents include receptor grain
Sub (such as acceptor bead) and/or donor particle (such as donor bead).
On the other hand, the present invention relates to a kind of manufactures doped with the method for the polymer optical fiber of acceptor dye composition, institute
The method of stating includes：Make the inner surface of polymer optical fiber and chemiluminescence singlet oxygen receptor (such as oxathiene) and following
At least one contact：(i) fluorescent chemicals (such as lanthanide series chelating agent, such as organic dyestuff) and (ii) quantum dot.
On the other hand, the present invention relates to a kind of manufactures doped with the method for the polymer optical fiber of donor dye composition, institute
The method of stating includes：Make the inner surface and photosensitising agent of polymer optical fiber.
Another party of the present invention is readily applicable to the description of the element (such as feature of system) of one aspect of the invention
The element (such as feature of equipment or method) in face.
Description of the drawings
With reference to schema and claims described below, the purpose of the present invention and feature may be better understood.
Fig. 1 is to describe according to an illustrative embodiment, for the doping in analyte detection system described herein
There is the schematic diagram of the hollow polymer optical fiber of acceptor dye.
Fig. 2 is to describe according to an illustrative embodiment, for the doping in analyte detection system described herein
There is the schematic diagram of the hollow polymer optical fiber of donor dye.
Fig. 3 is to describe according to an illustrative embodiment, by optical fiber, fiber optic bundle that optical fiber as shown in Figure 1 is formed
Schematic diagram, wherein each optical fiber is doped with acceptor dye.
Fig. 4 is to describe according to an illustrative embodiment, by optical fiber, fiber optic bundle that optical fiber as shown in Figure 2 is formed
Schematic diagram, wherein each optical fiber is doped with donor dye.
Fig. 5 is described according to an illustrative embodiment, how to change the doping of hollow optical fiber to realize various spirits
Sensitivity is horizontal and allows the schematic diagram of the multiplexing between the different variants of specific antigen.
Fig. 6 is described according to an illustrative embodiment, and the schematic diagram of the chuck of number of polymers fiber optic bundle is included.
Fig. 7 is to carry out single analysis using hollow polymer optical fiber described herein according to an illustrative embodiment
The schematic diagram of object and/or the example system 700 of multiple analytes detection.
Fig. 8 A be according to an illustrative embodiment, power supply and comprising for detection and analysis come from hollow polymer optical fiber
The image of the electronic circuit board of the light detector system of the signal of system.
Fig. 8 B are according to an illustrative embodiment, including for detection and analysis from hollow polymer fibre system
The image of the electronic circuit board of the photodetector of signal.
Fig. 8 C are the one group of example avalanche photodide (avalanche shown according to an illustrative embodiment
Photodiode, APD) responsiveness curve figure.
Fig. 8 D are sections according to an example of the graphical user interface of the customization diagnostic software of an illustrative embodiment
Screen.
Fig. 9 is to carry out single analysis using hollow polymer optical fiber described herein according to an illustrative embodiment
The schematic diagram of object and/or the example system of multiple analytes detection.
Figure 10 is to carry out single analysis using hollow polymer optical fiber described herein according to an illustrative embodiment
The schematic diagram of object and/or the example system of multiple analytes detection.
Figure 11 is shown according to an illustrative embodiment, including optical fiber encloser module is attached to single detection unit module
System and be attached to comprising optical fiber encloser module two detection unit modules system schematic diagram.
Figure 12 A are according to an illustrative embodiment, for detecting the signal from hollow polymer optical fiber to carry out list
One and/or multiple analytes detection example system image.
Figure 12 B are according to an illustrative embodiment, for detecting the signal from hollow polymer optical fiber to carry out list
One and/or multiple analytes detection example system image.
Figure 13 is described according to an illustrative embodiment, the bead and autoreceptor dye emission of excitation doping donor dye
The schematic diagram of light.
Figure 14 is according to an illustrative embodiment, for obtaining sample and being divided by hollow polymer fibre system
The figure of the method for analysis.
Figure 15 A are to include the image of the polymer optical fiber of multiple hollow cores according to an illustrative embodiment.
Figure 15 B are to include the image of the polymer optical fiber of multiple hollow cores according to an illustrative embodiment.
Figure 15 C are to include the image of the end face of the polymer optical fiber of multiple hollow cores according to an illustrative embodiment.
Figure 16 is a group picture of the hollow polymer optical fiber that connector and syringe are connected to according to an illustrative embodiment
Picture.
Figure 17 A are displays according to an illustrative embodiment, the hollow polymer fibre optical transmission light of auto-dope acceptor dye
Image.
Figure 17 B be display according to an illustrative embodiment, from the image of hollow polymer fibre optical transmission light, wherein away from
A part of optical fiber in optical fiber end shorter (1 to 2cm) distance is doped with acceptor dye composition.
Figure 17 C are displays according to an illustrative embodiment, are transmitted along hollow polymer optical fiber and from the undoped of optical fiber
Hold the image of the transmitting light left.
Figure 18 A are according to an illustrative embodiment, from undoped optical fiber, the optical fiber of europium doped chelating agent and europium doped
The image of the section transmitting light of the optical fiber of chelating agent and oxathiene.
Figure 18 B are displays according to an illustrative embodiment, from undoped optical fiber, europium doped chelating agent optical fiber and mix
The screenshotss for the light-emitting data that the section of the optical fiber of miscellaneous europium chelating agent and oxathiene obtains.
Figure 18 C are the letters from the transmitting detected from the fiber segment of different doping according to an illustrative embodiment
Number figure.
Figure 19 is the block diagram of the exemplary cloud computing environment used in some embodiments.
Figure 20 is the block diagram of the EXEMPLARY COMPUTING DEVICE used in some embodiments and example mobile computing device.
Specific implementation mode
It is expected that the equipment of the disclosure, system, method and technique cover using embodiment described herein information institute into
Capable change and modification.Those possessing an ordinary skill in the pertinent arts can to equipment described herein, system, method and technique into
Row reorganization and/or modification.
By System describe be have including or comprising specific components, or by technique and method be described as having including or
Including in the entire description of particular step, it is also contemplated that in the presence of this public affairs for being mainly made of the component or being made of the component
The system opened, and there is the technique according to the disclosure for being mainly made of the processing step or being made of the processing step
And method.
It should be understood that the order of step or order for executing certain actions are not important, as long as the technique is operable
.In addition, two or more steps or action can be carried out at the same time.
Herein any publication for example mentioned in the background section be not an admission that the publication serve as about
The prior art of any one of claim provided in this article.Background technology part is to provide for purposes of clarity,
Rather than it is intended as the description to the prior art about any claim.
Topic headings provided herein are for convenience.These titles are not intended to limit embodiment described herein
Range.
When specified chemical species referred to herein, it should be understood that the appropriate substitution or unsubstituted including the species
Form, and the form suitably to metallize comprising such as zinc, copper, aluminium, silicon, titanium, ferrimanganic, cobalt and nickel.
This disclosure relates to (" alpha ") technology is analyzed based on existing amplification Luminescent Proximity Homogenous, but using doped with mesh
It is preceding in existing alpha systems for " acceptor bead " (such as oxathiene, anthracene, rubrene and/or lanthanide series chelating
Agent) or the hollow polymer optical fiber of compound of " donor bead " (such as phthalocyanine) carry out single analysis analyte detection or multiplexing
Analyze method, system and the equipment of analyte detection.The signal that polymer optical fiber carrying is generated by dopant by singlet oxygen channel,
The signal be detected and used to differentiate in given sample the presence of of interest a kind of analyte or multiple analytes and/or
Amount.
I. hollow core polymer optical fiber
Polymer optical fiber is embedded with the known chemical reagent for allowing that luminescent oxygen channel is generated near complementary nano-particle.It lifts
For example, as used in telecommunications industry, polymer optical fiber can be by polystyrene and/or poly- (methyl methacrylate)
(PMMA) it is made.In certain embodiments, optical fiber it is shorter (be, for example, less than 5cm, be less than 3cm, be less than 2cm, or 1 with 3cm it
Between).In certain embodiments, optical fiber is extremely narrow, for example, optical fiber respectively have 0.1 to 2mm, such as 0.5 to 2mm, such as 1 to
The internal diameter (ID) of 1.5mm and/or 1 to 3mm, for example, 1.5 to 2mm outer diameter (OD).
In certain embodiments, the size of optical fiber enable optical fiber by capillarity by liquid (such as comprising waiting for
The sample solution of test sample) it sucks in its inside.In certain embodiments, the internal diameter that optical fiber respectively has keeps capillary to make
Liquid (such as wrapping solution with sample) is sucked in the inside of polymer optical fiber will pass through capillarity.
In certain embodiments, optical fiber has multiple hollow cores (such as 5 to 20 hollow cores).In certain embodiments,
The internal diameter (ID) of each hollow core of optical fiber with multiple hollow cores be 0.1 to 2mm, such as 0.5 to 2mm, such as 1 to
1.5mm.In certain embodiments, the size of each hollow core enables optical fiber (such as to wrap liquid by capillarity
Sample solution containing sample to be tested) it sucks in its inside (such as in each hollow core).In certain embodiments, optical fiber is every
The internal diameter that a hollow core has keeps capillarity will pass through capillarity by liquid (such as wrapping solution with sample)
It sucks in the inside of polymer optical fiber.
Polymer optical fiber can be doped using known technology, such as polymer is made to be expanded in dye solution, then
Be quickly cooled down so that polymer shrink and by dyestuff retention in the polymer matrix.In addition, in some embodiments it is possible to poly-
Introduce during closing object fiber manufacturing rather than later dopant.
Depending on embodiment, given polymer optical fiber can be doped with alpha technologies " receptor " dyestuff, such as oxygen thia ring
Hexene, anthracene, rubrene and/or lanthanide series chelating agent, such as europium chelating agent, terbium chelating agent, dysprosium chelating agent, samarium chelating agent, ytterbium
Chelating agent, erbium chelating agent and/or thulium chelating agent and/or its version；Or alpha technologies " donor " dyestuff, such as phthalocyanine,
Naphthalene phthalocyanine, chlorin, porphines, porphyrin, stellacyanin, chlorophyll, Bengal rose red and/or its version.
In certain embodiments, polymer optical fiber includes doped with acceptor dye composition, the acceptor dye composition
Chemiluminescence singlet oxygen receptor (such as oxathiene) and fluorescent chemicals (such as organic dyestuff (such as it is anthracene, red glimmering
Alkene), lanthanide series chelating agent (such as comprising lanthanide series, such as europium, terbium, dysprosium, samarium, ytterbium, erbium and thulium).
It is not intended to be fettered by specific theory, in certain embodiments, chemiluminescence singlet oxygen receptor (such as oxygen thia ring
Hexene) it is reacted with singlet oxygen, and generate ultraviolet light (such as light that wavelength is 340nm).Fluorescent chemicals are by chemiluminescence list
Line state oxygen acceptor is reacted with singlet oxygen and the ultraviolet excitation that generates, and emits fluorescence.In certain embodiments, energy passes through
Foster Resonance energy transfer (Resonance energy transfer, FRET) mechanism chemically shine singlet
Oxygen acceptor is directly transferred to fluorescent chemicals.Energy chemically shine singlet oxygen receptor be transferred to fluorescent chemicals will excite it is glimmering
Optical compounds cause the transmitting of fluorescence.
In certain embodiments, optical fiber is doped with quantum dot (such as fluorescence quantum).In certain embodiments, optical fiber is mixed
The miscellaneous acceptor dye composition for having quantum dot and including chemiluminescence singlet oxygen receptor.In certain embodiments, quantum dot exists
After being reacted generated ultraviolet light emission excitation with singlet oxygen by chemiluminescence singlet oxygen receptor, emit fluorescence.At certain
In a little embodiments, optical fiber is doped with quantum dot and includes chemiluminescence singlet oxygen receptor and fluorescent chemicals (such as group of the lanthanides member
Plain chelating agent) acceptor dye composition.
In certain embodiments, in existing alpha technological systems donor bead or acceptor bead it is identical, hollow optical fiber
Inside through coating and functionalised.For example, hollow optical fiber can include by glucan (such as two layers or two layers with
Upper glucan) polystyrene core surrounded, the outermost layer of glucan participates in Bioconjugation.Coating can use-NH2、-SH、-
COH ,-COOH and/or-CO-OR group functionalizations.Coating prevents dyestuff from leaching polymer.
In certain embodiments, the polymer optical fiber of array so doping/coating, which is assembled into, for example divides for multiplexing
Analyse the module or cassette in quality testing examining system.
In certain embodiments, the system needs excitation light source and detector.Hand-held or laboratory/experimental bench detection
Excitation light source in device may include such as laser, light emitting diode (LED) or lamp.For hand-held or laboratory/experiment
The detector of platform detector may include such as charge coupled device (CCD), photomultiplier (PMT) and/or avalanche optoelectronic two
Pole pipe (APD).Existing detector system can be used for or be adapted for reading from hollow optical fiber described herein
Signal, such as the absorbance based on monochromator, fluorescence and/or luminescence detector/reader.
The analysis analyte detection that I.A is carried out using the optical fiber of doping acceptor dye
Fig. 1 is the one embodiment for describing the system 100 comprising the hollow polymer optical fiber 106 doped with acceptor dye
Schematic diagram.First combines collocation object 108 (such as antibody, be portrayed as Y-shaped with thick line in Fig. 1) to be coupled to the inner surface of optical fiber
On.In the embodiment of description, the solution of the sample containing analyte of interest 110 (being portrayed as small diamond shape in Fig. 1) is prepared,
And donor bead 114 (being portrayed as circle) is added into the solution, such as be embedded with ' donor dye ' such as phthalocyanine coating it is anti-
The donor bead of raw albumen streptavidin.Second combination collocation object 112 (such as secondary antibody, it is portrayed as " Y " with filament in Fig. 1
Shape) it is coupled to donor bead, described second combines collocation object to be for example biotinylated.Solution is inhaled into optical fiber and (such as passes through hair
Tubule power) in.Analyte 110 is using antibody to capturing to establish sandwich assay.In certain embodiments, biotinylated anti-
Body (secondary antibody) is bound to the epitope in analyte, and first antibody is bound to different epitopes.Streptavidin and
Compound is pulled together by biotin, keeps donor bead neighbouring.
Hollow optical fiber 106 is positioned in reader and is exposed to exciting light 102 (such as from laser), such as is passed through
The laser of the 680nm wavelength of optical fiber transmission.Excitation makes donor bead 114 discharge singlet oxygen 116, and the singlet oxygen is advanced more
Of about 200nm, thus allow to analyze larger complex molecule.When make donor particle by relevant molecule interaction (such as
Antigen-IgG interaction) neighbouring ' receptor ' hollow optical fiber when, then lanthanide series is generated in covering when being exposed to exciting light
Fluorescence 104 (or other acceptor dye fluorescence).When there are when analyte 110, acceptor dye generates light hair in polymer optical fiber 106
Penetrate 104；Photoemissive intensity changes (such as proportional to analyte concentration) with analyte concentration.
Figure 13 is to describe the example system 1300 for including the hollow polymer optical fiber 106 doped with acceptor dye composition
Another schematic diagram.The donor bead 114 being shown in similar to Fig. 1, Figure 13 in hollow polymer optical fiber.By means of being bound to optical fiber
106 inner surface first combine collocation object, analyte of interest and be coupled to donor bead 114 second combine collocation object it
Between relevant molecule interaction, make the inside of the hollow polymer optical fiber 106 of the neighbouring doping acceptor dye of donor bead 114.
When being exposed to exciting light 102 (such as laser excitation of 680nm wavelength), donor bead discharges singlet oxygen 116 so that mixes certainly
The optical fiber 106 of miscellaneous acceptor dye emits light 1360.Exactly, in the example shown in fig. 13, optical fiber is doped with including oxygen
The acceptor dye composition of thia cyclohexene 1320 and europium chelating agent 1340.Europium (Eu) chelating agent 1340 is by oxathiene
1320 react with singlet oxygen and are converted to 340nm light caused by derovatives and directly excite.The europium chelating agent being excited
1340 generations detectable strong light 1360 in narrow wavelength bandwidth centered on by about 615nm.
Fig. 1 describe (and can distinguish) different from the wavelength of exciting light 104 wavelength (such as 520nm and 620nm it
Between, for example, 615nm) transmitting light 102.It is detected and determines the presence of analyte to transmitting light, and/or based on detected
Optical signal, the amount of analyte in sample is quantified.
Bead described herein can use organic or inorganic material, such as glass, metal, latex, synthesis or naturally deposit
Polymer such as polystyrene, makrolon, silicon, nylon, cellulose, agarose, glucan and polyacrylamide prepare.Grain
Son can be latex bead.In certain embodiments, bead is grade, micron order or nano level.In certain embodiments,
Use the particle different from bead form.
The particle used in bead analysis may include the functional group for being bound to amplicon.For example, certain
In embodiment, particle may include carboxyl, amine, amino, carboxylate, halogen, ester, alcohol, carbamide, aldehyde, chloromethyl, sulphur oxidation
Object, nitrogen oxides, epoxy group and/or tosyl functional group.Amplicon is bound to the particle that particle generates coding.
In certain embodiments, the laser pulse of the system transmission 680nm (or other excitation wavelengths) is to excite embedding
There is the covering (or being embedded with the nano-particle of polystyrene) of phthalocyanine and generates singlet oxygen.Hollow optical fiber carrying passes through singlet
The excitation of oxygen channel is containing lanthanide series chelating agent through signal caused by embedded nano particle or covering.In some embodiments
In, the wavelength of exciting light is 775nm, corresponds to the excitation wavelength of naphthalene phthalocyanine (another example of photosensitizer).
In certain embodiments, launch wavelength depends on the selection of acceptor dye composition.For example, europium emits
The wavelength of 615nm, dysprosium emit the wavelength of 575nm, and samarium emits the wavelength of 645nm, and the wavelength of terbium transmitting 545nm.
The analysis analyte detection that I.B is carried out using the optical fiber of doping donor dye
Fig. 2 is the schematic diagram of system 200 of the description comprising the hollow polymer optical fiber 206 doped with donor dye, and
It is the version of embodiment shown in Fig. 1.In certain embodiments, optical fiber is doped with including photosensitizer (such as phthalocyanine, naphthalene phthalein
Cyanines, chlorin, porphines, porphyrin, stellacyanin chlorophyll and/or Bengal rose red) donor dye composition, it is described
Photosensitizer is when with exciting light (such as the light of wavelength in the visible spectrum, such as light of the wavelength near infrared spectrum, such as wavelength
The light of 680nm, such as wavelength is the light of 775nm) irradiation when discharge singlet oxygen.
In fig. 2, it is coated with to combine doped with hollow polymer ' donor ' optical fiber 206 of donor dye (such as phthalocyanine) and take
With object 108 (such as antibody, be shown as Y shape in fig. 2).Be embedded with acceptor dye (such as oxathiene and/or group of the lanthanides member
Plain chelating agent) ' receptor ' nano-particle 214 (such as polystyrene bead, be shown round in fig. 2) be coated with it is different
In conjunction with collocation object 112 (such as different antibodies).When interacted by relevant molecule (such as antigen-IgG interaction) make by
When body nano-particle is adjacent to ' donor ' hollow optical fiber, exciting light (such as under excitation wavelength, such as 680nm, such as 775nm) swashs
Send out donor optical fiber so that acceptor nanoparticles generate fluorescence (such as lanthanide series fluorescence).Excited donor optical fiber causes donor light
Fibre release singlet oxygen 216.Pass through relevant molecule interaction (such as antigen-IgG interactions) neighbour when making acceptor particles 214
When nearly donor hollow optical fiber 216, then when being exposed to exciting light, acceptor particles generation lanthanide series fluorescence 104 (or other receptors
Dye fluorescence).When there are when analyte 110, acceptor dye generates light emitting 104 in acceptor particles 214；Photoemissive intensity with
Analyte concentration and change (such as proportional to analyte concentration).Transmitting light is detected and determines the presence of analyte
And/or concentration.
I.C is multiplexed by polymer optical fiber Shu Jinhang
Fig. 3 is to describe the fiber optic bundle 300 (such as including 1 to 20 optical fiber) formed by optical fiber, optical fiber as shown in Figure 1
Schematic diagram, wherein each optical fiber is doped with " receptor " dyestuff.A variety of acceptor dyes can be used (such as using not in different optical fiber
Same dyestuff) so that as that can be distinguished above for the transmitting light generated described by Fig. 1, and thus may determine that multiple analytes
Presence and/or concentration.In certain embodiments, can be different with optical fiber in conjunction with collocation object, and may be deposited between each optical fiber
In other composition differences, thus allow to advanced optimize multiplexing analysis analyte detection.
Fig. 4 is the schematic diagram for describing the fiber optic bundle 400 formed by optical fiber, optical fiber as shown in Figure 2, wherein each optical fiber is mixed
It is miscellaneous to have " donor " dyestuff.Combination in donor dye, optical fiber is arranged in pairs or groups object, and different acceptor beads and composition can change with
Diacritic signal is generated, multiplexing analysis analyte detection is thus allowed.
I.D is multiplexed by single polymers optical fiber
Fig. 5 is the schematic diagram for the different instances (being referred to as 500) for describing hollow polymer optical fiber.Different instances illustrate as
What, which could change, is coupled to the different configurations of a variety of combinations collocation object of hollow optical fiber inner surface and/or combines the difference of collocation object
Concentration is to realize the multiplexing between various level of sensitivity and the different variants of permission specific antigen.For example, at certain
In a little embodiments, the different sections (such as first segment 522, second segment 524 and third section 526) of optical fiber 520 are coated with various concentration
The combination collocation object (such as IgG) of (such as surface concentration) is to realize various level of sensitivity, such as down to pg/ml.
In some embodiments, to allow to detect specific antigen in the different different sections for combining collocation object to can be used for given optical fiber 540
Different variants.For example, the first section 542 of optical fiber 540 is coated with the first combination collocation object for being bound to the first variant,
Second section 544 of optical fiber 540 is coated with the second combination collocation object for being bound to the second variant, and the third area of optical fiber 540
Section 546 is coated with the third combination collocation object for being bound to third variant.
In addition, in certain embodiments, the variation of the combination collocation species type and ratio that are used in given optical fiber 560 is permitted
Perhaps multiplexing analysis analyte detection is carried out in larger concentration range.For example, the first section 568 of optical fiber 560 includes three
A segmentation 562,564,566 is respectively coated with the different of the different variants for being bound to analyte of interest and combines collocation object.
In first section 562 of optical fiber, described three are segmented the corresponding combination collocation for respectively containing the first ratio (such as higher rate)
Object.Other sections 570,580 of optical fiber also respectively contain three segmentations, are respectively coated with the segmentation phase with the first section 568
Same but different ratio combination collocation object.
I.E fiber optic bundle chucks
Fig. 6 is the example system that description includes the chuck 620 containing multiple (such as 8 to 10) fiber optic bundles (being referred to as 630)
600 schematic diagram.In certain embodiments, multiplexing inspection is carried out to the analyte in multiple samples using fiber optic bundle chuck
It surveys.For example, for giving fiber optic bundle, such as 632 or 634, different optical fiber in fiber optic bundle can doped with it is different by
Body dye composite, and from different combinations collocation object coupling so as to by above for detecting a variety of points in a manner of described in Fig. 3
Analyse presence and/or the concentration of object.Similarly, in another example, each optical fiber in fiber optic bundle can be doped with donor dye
Composition, and can be using different acceptor beads so as to by above for detecting multiple analytes in a manner of described in Fig. 4
In the presence of and/or concentration.
In certain embodiments, each fiber optic bundle in chuck can be used for the analysis quality testing of the multiplexing in different samples
It surveys.Therefore, it is possible to use single chuck 620 detects the multiple analytes in multiple samples.In certain embodiments, the chuck
In each fiber optic bundle there is optical fiber (same fibre group) with other fiber optic bundle the same categories, such as each of chuck
Fiber optic bundle, the concrete configuration (such as acceptor dye or donor dye) for the dyestuff that the optical fiber in fiber optic bundle is adulterated and is coupled to light
The concrete configuration of the combination collocation object of the inner surface of optical fiber is identical as other fiber optic bundles in the chuck in fine beam.
In certain embodiments, it is (such as each to belong to different type for two or more fiber optic bundles in the chuck
The optical fiber of fiber optic bundle has different dyestuffs and combines the configuration of collocation object).Therefore, it is possible to use including different types of multiple light
The single chuck of fine beam carries out the multiplexing detection of multiple analytes in sample.In certain embodiments, make every in chuck
A fiber optic bundle is contacted with a part for same sample to be detected with the multiplexing for carrying out multiple analytes in sample.
In certain embodiments, chuck 620 can place (640) in the chuck reader 660 of the system to provide
Switching between fiber optic bundle, thus allow by it is a kind of it is convenient in a manner of detect the signal from each fiber optic bundle.
II. it is used for the detecting system of polymer optical fiber
II.A detecting system components
Fig. 7 is to carry out single analyte and/or multiple analytes detection using hollow polymer optical fiber described herein
Example system 700 schematic diagram.Sample, bead and reagent (such as from micro disk hole, bottle or other containers) 702 are introduced
In the inside of hollow optical fiber 720, for example, solution is to suck hollow optical fiber by capillary force.Laser diode 780 (or it is other
Light source) exciting light is provided, and detector 760 (such as including CCD, PMT and/or APD) measurement travels across optical fiber/along optical fiber
Thus the transmitting light of traveling differentiates the respective presence of one or more analytes and/or concentration in sample.
Fig. 8 A are the figures for a set of component of signal of the detection and analysis from hollow optical fiber system described herein
Picture.The component includes detection circuitry plate 802 and power supply 808 containing detector.Fig. 8 B are the inspections for showing detector 804
Survey the image of the reverse side of electronic circuit board 802.In the example of Fig. 8 A and Fig. 8 B, detector is avalanche photodide (APD).
In certain embodiments, other photoelectric detectors have been used, such as photodiode (PD), photomultiplier (PMT), light guide detection
Device.In certain embodiments, multi-element detector has been used, such as focal plane arrays (FPA) (FPA) (such as CCD, CMOS detector).
Detector (such as APD, PD, PMT) measurement travel across optical fiber/along optical fiber advance, be incident on detector active region
Transmitting light on domain.Detector (such as APD, PD, PMT) exports electric signal in response to the light being incident on its zone of action
(such as electric current).By power of the amplitude with the light being incident on the detector zone of action of the electric signal of detector output, incidence
The wavelength of light and the responsiveness (luminous sensitivity) of detector and change.Other factors, as (example is arranged in the gain of temperature, detector
As can be by means of across bias voltage that detector applies control gain setting) can also influence the electric signal exported by detector
Amplitude.
In general, the amplitude of the electric signal generated by detector and the power of light that is incident on its zone of action generally at
Ratio.The responsiveness (luminous sensitivity) of detector determines the light for the setted wavelength being incident on for per unit on its zone of action
Power, detector is by the amplitude (such as electric current) of the electric signal of generation.
Fig. 8 C show the example of the curve graph 860 of one group of responsiveness curve of display APD.Different curves 866,868 and
870 different gains for corresponding to APD are arranged.Curve 866,868 and 870 shows that per unit is incident in the power on APD and is produced
Raw electric current (such as with ampere/watt measurement).Peak response degree (luminous sensitivity) wavelength 880 of APD is present in about 620nm.
That is, wavelength, which is electric signal (such as electric current) caused by the light per unit of power of about 620nm, will be greater than having different waves
Long light.Light irradiation detector (such as APD) with wavelength much larger than peak response wavelength will be such that detector (such as APD) produces
Raw insignificant electric signal.
In order to keep detecting system maximum to the sensitivity for giving the light that acceptor dye composition is emitted, peak value can be selected
The response wave length detector consistent with the launch wavelength of acceptor dye composition (such as APD).In the example of Fig. 8 C, 620nm
Wavelength of peak sensitivity close to the launch wavelength of europium, i.e. 615nm.Can select different detectors (such as difference APD) so that
Best is reached to the sensitivity of the transmitting from different acceptor dye compositions.
Power supply supplies electric power to the electronic building brick (such as detector) of detecting system.In certain embodiments, the power supply
It is self contained, and includes battery.In certain embodiments, the bias plasma applied across detector is controlled using power panel
Pressure.In certain embodiments, bias voltage determines the gain setting of detector, thus promotes the detection of low-intensity incident light.
In certain embodiments, the system includes other electronic component, and the electronic component, which receives, carrys out self-detector
Signal (such as electric current), and export that represent the relative intensity for being incident in light on detector (such as big with the relative intensity
It is proportional on body) digitized signal.
In certain embodiments, the system includes customization diagnostic software.Diagnostic software reception, which corresponds to, carrys out self-detector
Signal data, the signal represents detected transmitting light.In certain embodiments, correspond to the letter for carrying out self-detector
Number data be to represent the relative intensity (such as generally proportional to the relative intensity) for being incident in light on detector
Digitized signal (such as being generated by the other electronic component of the system).Based on the signal data received, customization diagnosis
Software is provided the detection of one or more analytes carried out based on the signal received and/or quantified.Fig. 8 D are that customization diagnosis is soft
The example of the screenshotss 890 of the graphical user interface of part.
Fig. 9 and Figure 10 is to carry out single analyte and/or a variety of points using hollow core polymer optical fiber described herein
Analyse the schematic diagram of the example system 900 of analyte detection.In certain embodiments, the system include detector (such as APD, CCD,
PMT), and as above for power supply described in Fig. 8 A.
II.B optical fiber mounting brackets
In certain embodiments, the system includes for keeping polymer optical fiber and/or polymer optical fiber beam 904 and making
Its optical fiber mounting bracket 902 with detector in line.For example, when optical fiber is positioned in optical fiber mounting bracket, optical fiber peace
Shelve keep optical fiber so that the axis of optical fiber it is straight enough and with detector concentric (such as the axis of optical fiber and detector active region
The center in domain is aligned).Similarly, the fiber optic bundle 904 being placed in mounting bracket be held so that fiber optic bundle axis enough it is straight simultaneously
And (such as the axis of fiber optic bundle is aligned with the center of the detector zone of action) concentric with detector.By this method, it advances along optical fiber
Transmitting light 906 (such as from the optical fiber doped with acceptor dye, such as the acceptor bead in optical fiber) the one of optical fiber
Optical fiber is left at end, towards detector line into and be incident on the detector zone of action.In certain embodiments, light is left in detection
The transmitting light of fine end provides the transmitting light for being incident in the maximum intensity on detector, thus makes the signal that detector generates most
Greatly.As above for described by Fig. 1 and Fig. 2, transmitting light can be by the optical fiber and/or optical fiber doped with acceptor dye composition
Acceptor bead generate.
II.C shells
In certain embodiments, the system includes shell 920, surrounds detector, optical fiber mounting bracket and is placed on peace
Optical fiber in shelving and/or fiber optic bundle.The offer of shell 920 is substantially non-transparent case to ambient light, thus prevents ambient light
Irradiating and detecting device 908 and/or optical fiber and/or fiber optic bundle 904.
II.D excites port
In certain embodiments, shell includes one or more excitation ports, and the exciting light from excitaton source can be guided
Across the excitation port (such as the excitaton source of optical fibre coupling can connect the ports SMA).In certain embodiments, end is excited
One of mouth is axial excitation port 942.Axial excitation port 942 and detector 908 and the light being placed in optical fiber mounting bracket 902
Fine and/or fiber optic bundle 904 axis is concentric.When optical fiber to be positioned in optical fiber mounting bracket 902, it is guided through axial excitation end
The exciting light 946 of mouth 942 is advanced in the direction upper edge optical fiber of detector 908, thus irradiation optical fiber.Similarly, when by fiber optic bundle
904 when being positioned in optical fiber mounting bracket 902, is guided through the exciting light 946 of axial excitation port 942 in detector 908
One or more optical fiber in the upper edge fiber optic bundle of direction are advanced.
In certain embodiments, one of excitation port is orthogonal with excitation port 944.The orthogonal process pair of excitation port 944
Standard is with orthogonal with the axis for the optical fiber and/or fiber optic bundle 904 being placed in optical fiber mounting bracket 902.It is guided through quadrature exciting end
The exciting light of mouth 944 is placed on along the direction orthogonal with the axis of optical fiber and/or fiber optic bundle 904, direction in optical fiber mounting bracket 902
Optical fiber and/or fiber optic bundle 904 are advanced.Therefore, the exciting light for being guided through quadrature exciting port 944 is pacified across optical fiber is placed on
The optical fiber in 902 is shelved, thus irradiation optical fiber.Similarly, when fiber optic bundle 904 to be positioned in optical fiber mounting bracket 902, drawn
Lead across quadrature exciting port 942 exciting light pass through fiber optic bundle 904 one or more optical fiber, thus the one of irradiation optical fiber beam or
Multiple optical fiber.
In certain embodiments, shell 920 includes axial excitation port.In certain embodiments, shell 920 includes orthogonal
Excite port.In certain embodiments, shell 920 includes two or more quadrature exciting ports.In certain embodiments,
Shell 920 includes two quadrature exciting ports and an axial excitation port.
In certain embodiments, excitation port is configured to connect to optical fiber (different from hollow polymeric described herein
Object light is fine), to receive the exciting light from optical fibre coupling excitaton source.For example, excitation port can be the ports SMA.
In some embodiments, excitation port is sealing (such as being sealed by lid) when not in use, outer to prevent ambient light from entering
In shell 920.
In certain embodiments, excitaton source is in the outside of shell 920.For example, external laser diode can be used
As excitaton source.In certain embodiments, shell 920 surrounds excitaton source and detector, optical fiber mounting bracket and is placed on installation
Optical fiber in frame and/or fiber optic bundle, thus the system is self contained system (such as pocket system, such as hand-held system
System).
II.E optical fiber
In certain embodiments, the system includes optical filter 960, and the optical filter is to the light base with excitation wavelength
It is opaque and transparent to the light of the wavelength with acceptor dye launch wavelength in sheet.Optical filter 960 is placed on detector 908
Front, thus prevent exciting light (such as 946) irradiating and detecting device from excitaton source, at the same allow emit light 906 by simultaneously
Irradiating and detecting device 908.The transmissivity of optical filter corresponds to the score for the light for being incident on optical filter and being transmitted through optical filter, and
And change with the wavelength of light.Different optical filters with different transmissivities are transparent to the light of different wave length and opaque and can
With depending on the difference adulterated for the specific excitaton source and optical fiber and/or acceptor bead of irradiation optical fiber and/or fiber optic bundle
Special receptor dye composite and use.Optical filter can be installed by changeable mode, thus be cut optical filter
It changes, such as to detect the transmitting from special receptor dye composite and/or to block the exciting light from given excitaton source.
The various elements of II.E
In certain embodiments, the system includes electronic building brick associated with detector and power supply, and jacket
The size of shell 920 is configured to accommodate other electronic building brick and electric wire.
In certain embodiments, the system includes the power connector 1040 for being connected to external power supply.Certain
In embodiment, the system includes for being connected to the interface 1020 of external computing device (such as desktop computer) (such as USB
Port).Ambient light enters in shell 920 in order to prevent, and various interfaces, port and power connector are sealed with gasket.
II.F chuck readers
In certain embodiments, the system includes the letter for sequentially reading multiple fiber optic bundles from fiber optic bundle chuck
Number chuck reader.Particular fiber beam in chuck is maintained at active position to be irradiated and be examined with exciting light by chuck reader
Survey the transmitting light of the optical fiber from fiber optic bundle.Particular fiber beam in active position is held so that fiber optic bundle axis is flat enough
Direct join and concentric with detector (such as the axis of fiber optic bundle is aligned with the center of the detector zone of action).By this method, along optical fiber
The transmitting light (such as from the optical fiber doped with acceptor dye composition, such as the acceptor bead in optical fiber) of traveling is in light
Fine at one end leaves optical fiber, towards detector line into and be incident on the detector zone of action.
Chuck reader provides the mechanical switch being maintained between each fiber optic bundle in active position.In some embodiments
In, the first fiber optic bundle in chuck is maintained at active position, and exciting light is used in combination to irradiate.The light is come from by detector detection
The transmitting light of fine beam.After detecting the transmitting light from the first fiber optic bundle, chuck reader switches out the first fiber optic bundle
Active position, and the second fiber optic bundle is switched in active position.Then the second fiber optic bundle is irradiated with exciting light, and passes through detection
Device detects the transmitting light from the second fiber optic bundle.
II.G modules configure
Figure 11 is turned to, in certain embodiments, the system includes the multiple modular units for being attached to each other and combining.At certain
In a little embodiments, the system includes optical fiber encloser module 1140 and one or more detection unit modules 1122.Optical fiber case mould
Block 1140 includes optical fiber mounting bracket 902, and optical fiber and/or fiber optic bundle are placed in the optical fiber mounting bracket.Optical fiber encloser module
1140 include the shell for surrounding optical fiber mounting bracket and the optical fiber and/or fiber optic bundle wherein placed.Optical fiber case 1140 also includes one
Or multiple excitation ports 942,944.Each detection unit module 1122 comprising detector and associated electronic components (such as power supply,
Such as interface board), and surround the shell of detector and associated electronic components.In certain embodiments, each detection unit mould
Block 1122 includes optical filter.
Optical fiber encloser module 1140 is attached to one or more detection unit modules 1122.In order to make to come from optical fiber encloser module
Optical fiber in 1140 emit light into detection unit module and the detector of irradiating and detecting unit module 1122, optical fiber case
Module 1140 includes when optical fiber encloser module is attached to detection unit module 1122 and the respective end of detection unit module 1122
The port of mouth alignment.
In certain embodiments, optical fiber encloser module 1140 includes two ports in the opposite end of optical fiber encloser module, by
This allows two detection unit modules to be attached to single optical fiber encloser module.
Figure 11 is to show the system (1120) that single detection unit module 1122 is attached to comprising optical fiber encloser module 1140
And the signal of the system (1180) of two detection unit modules 1122a and 1122b is attached to comprising optical fiber encloser module 1140
Figure.In certain embodiments, including the optical fiber encloser module 1140 of two ports is attached to single detection unit module 1122, and
And add-on module 1160 covers not used port to prevent ambient light from entering in system by optical fiber encloser module.In certain realities
It applies in example, add-on module 1160 includes axial excitation port 1162.
In certain embodiments, including the optical fiber encloser module 1140 of two ports is attached to first detection unit module
1122a and second detection unit module 1122b, the detection unit module respectively contain detector and associated electronic components.
In some embodiments, the first detector of first detection unit module 1122a and the second inspection of second detection unit module 1122b
Survey device belong to same type (such as the responsiveness of the first and second detectors to irradiate detector light wavelength have identical phase
Closing property).In certain embodiments, the first detector of first detection unit module 1122a and second detection unit module 1122b
The second detector belong to different type (such as the first and second detectors have with irradiating and detecting device light wavelength with difference
The different responsivenesses that mode changes).In certain embodiments, first detection unit module 1122a include the first optical filter and
Second detection unit module 1122b includes the second optical filter.In certain embodiments, the first optical filter belongs to the second optical filter
Same type (such as transmissivity is identical with the variation of the wavelength of the incident light of the first and second optical filters).In certain implementations
In example, the first optical filter and the second optical filter belong to different type (such as the transmissivity of the first and second optical filters are with optical wavelength
Change in different ways).
II.H system prototypes
Figure 12 A and Figure 12 B are for detecting the signal from hollow core polymer optical fiber to carry out single and/or a variety of point
Analyse two images of the example system 1200 of analyte detection.These image display systems 1200 are connected comprising optical fiber encloser module 1140
The not used port of optical fiber case unit 1140 is covered to single detection unit module 1122 and add-on module 1162.It is described
System includes external power supply, and three excitation ports for being connected to external stimulus.
In certain embodiments, the system is comprising self-contained power source (such as battery) and one or more excitaton source (examples
Such as one or more laser diodes) self contained system.In certain embodiments, all system components (such as power supply, detection
The optical fiber and/or fiber optic bundle of device, excitaton source, optical fiber mounting bracket and tested person) it is all packaged inside the shell.In some embodiments
In, the system is the self contained system of hand-held.In certain embodiments, the weight of the hand held system be no more than 1 to
2lbs.In certain embodiments, the total volume that the system occupies is no more than 750cm3.In certain embodiments, the system
Of length no more than 150mm.In certain embodiments, the width of the system is no more than 100mm.In certain embodiments, institute
The thickness for stating system is no more than 50mm.
The detection pattern of III multiplexing analysis analyte detections
The multiplexing detection and/or quantitative several system configurations for realizing analyte are possible.Utilize (i) different by
The different emission of body dye composite；(ii) the different excitation wavelengths of different donor dye compositions；And (iii) is different
Different spaces positioning of the optical fiber in fiber optic bundle, can provide different multichannel multiplexing methods.
III.A is detected using the multiplexing of different acceptor dye launch wavelengths
In certain embodiments, the multiplexing detection of different analytes can by diacritically detect come from it is different by
The transmitting light of body dye composite is realized.The hollow polymer fiber optic bundle doped with different acceptor dye compositions can be used,
And/or the acceptor bead doped with different acceptor dye compositions.As above with respect to described by Fig. 3, the different optical fiber in fiber optic bundle
Doped with different acceptor dye compositions and can changing with optical fiber in conjunction with collocation object for optical fiber inner surface can be coupled to.
Adulterate the optical fiber of acceptor dye
In certain embodiments, the multiplexing detection of different analytes can by diacritically detect come from it is different by
The transmitting light of body dye composite is simultaneously realized using the hollow polymer fiber optic bundle 300 doped with acceptor dye.Such as above with respect to
Described by Fig. 3, different optical fiber in fiber optic bundle 300 doped with different acceptor dye compositions and can be coupled to table in optical fiber
Face can change in conjunction with collocation object with optical fiber.
In an example, the first optical fiber 302 of fiber optic bundle is doped with the first acceptor dye with the first launch wavelength
Composition, and the second optical fiber 304 of fiber optic bundle is doped with the Co receptor dye composite with the second launch wavelength, it is described
Second launch wavelength is different from first launch wavelength.Exactly, different acceptor dye compositions, which generate, has different waves
Long transmitting light.For example, including the acceptor dye composition of europium emits 615nm wavelength；Include the acceptor dye combination of dysprosium
Object emits 575nm wavelength；Including the acceptor dye composition of samarium emits 645nm wavelength；And the acceptor dye combination comprising terbium
Object emits 545nm wavelength.By selective enumeration method emit the launch wavelength corresponding to special receptor dye composite it is specific
The light of wavelength, it is possible to authenticate go out the light emitted from the particular fiber doped with special receptor dye composite.Therefore, it can be based on
Emit the wavelength difference of light from the light of the different fibre optical transmissions doped with different acceptor dye compositions.
In order to detect presence and/or the concentration of different analytes, different molecular interaction will be undergone from different analytes
The different inside for combining collocation objects to be also coupled to different optical fiber.Exactly, it is coupled to mixing for the inner surface of the first optical fiber 302
It is miscellaneous to have the first optical fiber of the first acceptor dye composition that collocation object is combined to be bound to the first analyte.As retouched above with respect to Fig. 1
It states, when the first particle for being coupled to donor bead combines collocation object also in relation with to the first analyte, establishes sandwich assay.Cause
This, combines collocation object, the first analyte and the first particle that the interaction between collocation object is combined to establish by means of the first optical fiber
Sandwich assay make donor bead adjacent to the inner surface of the first optical fiber.When being irradiated with exciting light, donor bead is adjacent to the first light
302 the first acceptor dye compositions for being adulterated of fibre and the transmitting for causing the light of the first launch wavelength.Detect the first launch wavelength
Transmitting light thus allow detect the first analyte presence and/or concentration.
Similarly, the second optical fiber for being bound to the second analyte combines collocation object that can be coupled to doped with Co receptor dye
The inside of second optical fiber 304 of feed composition.It is coupled to the second particle and combines collocation object and also in relation with to the second analyte
Donor bead is by the second optical fiber combines the interaction between arranging in pairs or groups object in conjunction with collocation object, the second analyte and the second particle
The inner surface of neighbouring second optical fiber 304.Therefore, exciting light irradiation causes the transmitting of the light of the second launch wavelength, thereby indicates that the
The presence of two analytes and/or concentration
Therefore, by diacritically detecting the transmitting light of the first and second launch wavelengths, first and second points can be detected
Analyse object.The method can extend to the detection for realizing a variety of different analytes, wherein using corresponding optical fiber in fiber optic bundle is coupled to
The corresponding optical fiber of inner surface combine collocation object to capture each analyte.Each corresponding optical fiber is doped with transmitting distinct emission wavelength
Light unique receptor dye composite.Diacritically detection indicates respectively the presence of different analytes and/or the uniqueness of concentration
The light of launch wavelength is achieved in the presence to a variety of different analytes and/or the multiplexing detection of concentration.
Adulterate the optical fiber of donor dye
In certain embodiments, by doped with the different types of acceptor bead of different acceptor dye compositions with doped with
The optical fiber combination of donor dye composition is detected for multiplexing.The method is similar to previously described method, wherein optical fiber
Different optical fiber in beam respectively can be doped with different acceptor dye compositions, to realize the multichannel to a variety of unique analytical objects
Multiplexing detection.
Exactly, in certain embodiments, doped with the first acceptor dye composition (with the first launch wavelength)
There is the acceptor bead of the first kind the first particle collocation object to be combined to be coupled to its surface, and doped with Co receptor dye set
The acceptor bead of the Second Type of object (with the second launch wavelength different from the first launch wavelength) is closed with the second particle knot
It closes collocation object and is coupled to its surface.First particle combines collocation object to be bound to the first analyte, and the second particle combines collocation
Object is bound to the second analyte.As above for described by Fig. 2, when acceptor bead is (such as anti-by relevant molecule interaction
Original-IgG interaction) neighbouring ' donor ' optical fiber doped with donor dye composition when, pass through excitation donor optical fiber
And acceptor nanoparticles is made to generate transmitting light (such as fluorescence, such as lanthanide series fluorescence).
Exactly, donor coating optical fibers have the first optical fiber for capturing the first analyte to combine collocation object.When being coupled to
When first particle of the acceptor bead of one type combines collocation object also in relation with to the first analyte, the acceptor bead of the first kind by
This neighbouring donor optical fiber by means of the presence of the first analyte.Therefore, excited donor optical fiber makes the acceptor bead of the first kind
Light of the grain transmitting with the first launch wavelength.Similarly, when the second particle for being coupled to Second Type acceptor bead combines collocation
When object is also in relation with to the second analyte, the donor optical fiber for being coated with the second optical fiber combination collocation object for capturing the second analyte causes
The foundation of sandwich assay.Excited donor optical fiber makes the Co receptor dye composite transmitting that Co receptor bead type is adulterated
Light with the second launch wavelength.Therefore, identical as the previously discussed doping optical fiber of acceptor dye, emit the first launch wavelength
Light indicate the first analyte presence and/or concentration, transmitting the second launch wavelength light indicate the second analyte presence and/
Or concentration.Therefore, by diacritically detecting the transmitting light of the first and second launch wavelengths, the first and second analyses can be detected
The presence of object and/or concentration.
Similar to the optical fiber of doping receptor, the method can extend to the detection for realizing a variety of different analytes.In receptor
In the case of bead and donor optical fiber, each analyte is bound to the corresponding particle being coupled to the surface of the acceptor bead of respective type
In conjunction with collocation object.Unique receptor dye combinations of the acceptor bead of each respective type doped with the light of transmitting distinct emission wavelength
Object.Diacritically detection indicates respectively the light of the presence of different analytes and/or a variety of distinct emission wavelength of concentration, thus real
The now presence to a variety of different analytes and/or the multiplexing of concentration detect.
In certain embodiments, there are single donor optical fiber a variety of different optical fiber collocation object to be combined to be coupled to its interior table
Face, the optical fiber combine collocation object respectively to capture different analytes.Respectively doped with distinct emission wavelength it is unique by
The different types of acceptor bead of body dye composite is coated with different particles and combines collocation object, is respectively bound to different
Analyte.In certain embodiments, using donor fiber optic bundle 400, wherein each donor optical fiber, which has, captures different analytes
Different optical fiber combine collocation object to be coupled to its inner surface.
System component
In certain embodiments, the differentiation between first and second launch wavelength can by using multiple detectors and/
Or optical filter is realized.It for example, as described above, can be by diacritically detecting the hair with the first and second wavelength
Penetrate presence and/or concentration that light determines the first and second analytes respectively.Therefore, it is possible to use peak response degree is sent out close to first
The transmitting light of first the first launch wavelength of detector selective enumeration method of ejected wave length, and therefore detect the presence of the first analyte.
Can use peak response degree close to second the second launch wavelength of detector selective enumeration method of the second launch wavelength transmitting light,
And therefore detect the presence of the second analyte.
Similarly, the sensitive detector of the light of the first and second launch wavelengths can be applied in combination with two optical filters.
Exactly, transparent to the first launch wavelength and first optical filter opaque to the second launch wavelength can be placed on detection
The front of device passes through the light with the first launch wavelength so as to selectivity.Similarly, transparent to the second launch wavelength and to
The second opaque optical filter of one launch wavelength is placed in front of detector passes through the light with the second launch wavelength by selectivity.
Therefore, the signal generated by detector when the first optical filter is in place will indicate the presence of the first analyte and/or dense
Degree, and the signal generated by detector when the second optical filter is in place will indicate the presence of the second analyte and/or dense
Degree.
Multiple detectors can be applied in combination with multiple optical filters most preferably to distinguish first and second launch wavelength
Light, and convenience and/or measuring speed are improved (such as by avoiding switching between different optical filters and/or detector
Demand).
For example, in certain embodiments, the system includes and belongs to same type (such as to have the light of different wave length
Have same response degree) but it is placed with the first and second detectors of different optical filters in front.It is placed in front of the first detector
The first optical filter it is transparent to the light with the first launch wavelength and opaque to the light with the second launch wavelength.It is placed on
The second optical filter in front of two detectors it is transparent to the light with the second launch wavelength and to the light with the first launch wavelength not
It is transparent.Therefore, it is possible to use diacritically parallel (such as simultaneously) the first and second transmitted waves of detection of the first and second detectors
Long light.
Corresponding receptor is come from some embodiments it is possible to diacritically be detected by multiple detectors and/or optical filter
Multiple unique launch wavelengths of dye composite.In certain embodiments, each launch wavelength is detected using corresponding detector
Light.In certain embodiments, each corresponding detector belongs to different type.In certain embodiments, each corresponding detection
Device belongs to same type, but unique respective filter is placed in front of it.In certain embodiments, the system includes single
One detector and multiple optical filters, wherein each optical filter correspond to individual launch wavelengths and it is transparent to the launch wavelength and
It is opaque to the light of other launch wavelengths.
In certain embodiments, the single detector with multiple pixels has been used, and has been placed in the front of detector
There are dispersive optical elements (such as prism, such as grating).Dispersive optical elements reflect light depending on optical wavelength and with different angle,
And the light of different wave length is thus made to be incident on the different location of detector.Therefore, each to emit by using dispersive optical elements
The different respective groups of pixels of the light irradiation detector of wavelength, and the signal designation difference analyte from each respective groups of pixels
Presence and/or concentration.
III.B is detected using the multiplexing of different donor dye excitation wavelengths
In certain embodiments, presence to analyte and/or dense can also be realized by using different donor dyes
The multiplexing of degree detects.By with different respective wavelengths light irradiation can selective excitation have uniqueness excitation wavelength
Different donor dye compositions, be achieved in the presence to different analytes and/or the multiplexing of concentration detection.
Adulterate the optical fiber of donor dye
Exactly, in certain embodiments, the different optical fiber in fiber optic bundle doped with unique excitation wavelength not
With donor dye composition.In an example, the first optical fiber 402 in fiber optic bundle 400 is doped with the first excitation wavelength
The first donor dye composition, and the second optical fiber 404 in fiber optic bundle 400 is doped with second with the second excitation wavelength
Donor dye composition, second excitation wavelength are different from first excitation wavelength.With swashing with the first excitation wavelength
The first donor dye composition that the first optical fiber of irradiation optical fiber Shu Jifa 402 that shines is adulterated, but 404 institute of the second optical fiber is not excited
Second donor dye composition of doping.Therefore, when being irradiated with the exciting light with the first excitation wavelength, the first optical fiber 402
Interior acceptor bead, which will generate, emits light, but the second optical fiber 404 then cannot.Similarly, the irradiation optical fiber under the second excitation wavelength
The second donor dye that the second optical fiber of Shu Jifa 404 is adulterated, but the first donor dye for not exciting the first optical fiber 402 to be adulterated
Material.Therefore, when being irradiated with the exciting light with the second excitation wavelength, the acceptor bead in the second optical fiber 404 will generate transmitting
Light, but the first optical fiber 402 then cannot.
The inner surface of first optical fiber 404 is combined collocation object coupling, and second with the first optical fiber for capturing the first analyte
The inner surface of optical fiber 402 is combined collocation object coupling with the second optical fiber for capturing the second analyte.Acceptor bead, which is coated with, to be bound to
First particle of the first analyte combines collocation object.Therefore, it in the presence of the first analyte, is coated with the first particle and combines collocation
The acceptor bead of object combines mutual between collocation object, the first analyte and the first particle combination collocation object by means of the first optical fiber
It acts on and the inner surface of neighbouring first optical fiber 402.Similarly, it in the presence of the second analyte, is coated with and is bound to the second analysis
Second particle of object combines the acceptor bead of collocation object to combine collocation object, the second analyte and the second particle by means of the second optical fiber
The inner surface of neighbouring second optical fiber 404 in conjunction with the interaction between collocation object.
Therefore, the transmitting that the acceptor bead in the first optical fiber 402 is generated in response to the exciting light with the first excitation wavelength
Light indicates presence and/or the concentration of the first analyte.Acceptor bead in second optical fiber 404 is in response to having the second excitation wavelength
Exciting light generate transmitting light indicate the second analyte presence and/or concentration.
Adulterate the optical fiber of acceptor dye
In certain embodiments, the difference doped with the different donor dye compositions with different excitation wavelengths has been used
Donor bead realizes the multiplexing detection of analyte.Exactly, it is contaminated doped with the first donor with the first excitation wavelength
There is the first kind donor bead of feed composition the first particle collocation object to be combined to be coupled to its surface.It is contaminated doped with the second donor
The Second Type donor bead of feed composition (with the second excitation wavelength different from the first excitation wavelength) is with the second particle
It is coupled to its surface in conjunction with collocation object.First particle combines collocation object to be bound to the first analyte, and the second particle is combined and taken
It is bound to the second analyte with object.
The optical fiber for adulterating acceptor dye for combining collocation object to be coupled to inner surface with the first optical fiber captures the first analyte,
And thus make the inner surface of the donor bead adjacent fiber of the first kind.Similarly, there is the second optical fiber to combine collocation object coupling
Optical fiber to the doping acceptor dye of inner surface captures the second analyte, and thus makes the donor bead adjacent fiber of Second Type
Inner surface.
In certain embodiments, there is the first optical fiber in fiber optic bundle the first optical fiber collocation object to be combined to be coupled to its inner surface
And there is the second optical fiber in the fiber optic bundle the second optical fiber collocation object to be combined to be coupled to its inner surface.First in fiber optic bundle
Therefore optical fiber captures the first analyte, thus make the donor bead of the first kind and its inner surface neighbouring, and in fiber optic bundle
Therefore second optical fiber captures the second analyte, thus make the donor bead of Second Type and its inner surface neighbouring.
First adulterated with the exciting light irradiation optical fiber Shu Jifa first kind donor beads with the first excitation wavelength
Thus donor dye composition causes the transmitting for the first optical fiber for carrying out auto-dope acceptor dye.Swashing with the first excitation wavelength
It shines and does not excite the second donor dye composition that the donor bead of Second Type is adulterated, and therefore the second optical fiber will not be rung
Ying Yu has the exciting light irradiation of the first excitation wavelength and generates transmitting light.Therefore, detect the first optical fiber in response to having
The exciting light of one excitation wavelength irradiates and the presence for emitting light the first analyte of instruction generated and/or concentration.Similarly, apparatus
There is the second donor dye combination that the exciting light irradiation optical fiber Shu Jifa Second Type donor beads of the second excitation wavelength are adulterated
Thus object causes the transmitting for the second optical fiber for carrying out auto-dope acceptor dye.Exciting light with the second excitation wavelength does not excite
The first donor dye composition that the donor bead of the first kind is adulterated, and therefore the first optical fiber will not be in response to having second
The exciting light of excitation wavelength irradiates and generates transmitting light.Therefore, detect the second optical fiber in response to the second excitation wavelength
Exciting light irradiates and the presence for emitting light the second analyte of instruction generated and/or concentration.
In certain embodiments, there are the optical fiber the first and second optical fiber collocation object to be combined to be coupled to its inner surface, and
And first and second donor bead can reside in the optical fiber.Swashed with the exciting light irradiation optical fiber with the first excitation wavelength
Send out the first donor dye composition that the first donor bead is adulterated, but the second donor for not exciting the second donor bead to be adulterated
Dye composite.The second donor that the second donor bead is adulterated is excited with the exciting light irradiation optical fiber with the second excitation wavelength
Dye composite, but the first donor dye composition for not exciting the first donor bead to be adulterated.Therefore, it detects in response to
The transmitting light of one excitation wavelength irradiation indicates presence and/or the concentration of the first analyte, and detects in response to the second excitation wave
The transmitting light of long irradiation indicates presence and/or the concentration of the second analyte.
System component
In certain embodiments, there is swashing for the different excitation wavelengths for corresponding to different donor dye compositions in order to provide
It shines, the system includes two or more different excitaton sources (such as different laser diode, such as different
LED), the light with different wave length is respectively generated.In certain embodiments, each different excitaton source is guided through described
The different excitation ports of system.
In certain embodiments, single excitaton source has been used to provide the exciting light of different excitation wavelengths.In some embodiments
In, the single excitaton source is tunable laser.In certain embodiments, the single excitaton source is to generate a series of wavelength
The broad band source of light, and using optical filter selective transmission corresponding to the certain wave of the excitation wavelength of different donor dye compositions
Long light.
The multiplexing detection of III.C use spaces positioning
Detect the transmitting from fiber optic bundle difference optical fiber
In certain embodiments, can also be by the different spatial based on each optical fiber in fiber optic bundle, it will be from fiber optic bundle
In each fibre optical transmission light map in focal plane arrays (FPA) (such as CCD, such as CMOS cameras) different group one or more
In pixel, to realize the multiplexing detection of multiple analytes.Therefore, by focal plane arrays (FPA) respective sets it is one or more
A pixel diacritically in detection fiber beam the transmitting of each optical fiber light.
Different optical fiber in fiber optic bundle can have the different optical fiber for being bound to different analytes that collocation object is combined to be coupled to
Its inner surface.Therefore, the light of different fibre optical transmissions indicates presence and/or the concentration of different analytes in fiber optic bundle.By corresponding to
Light that first group of first optical fiber one or more pixels are detected (such as first group of pixel diacritically detects and comes from first
The light of optical fiber) thereby indicate that the first analyte that the first optical fiber for being coupled to the first optical fiber inner surface combines collocation object to be captured
In the presence of and/or concentration.Light (such as the second group of picture detected by second group of one or more pixel corresponding to the second optical fiber
Element diacritically detects the light from the second optical fiber) thereby indicate that the second optical fiber for being coupled to the second optical fiber inner surface combines collocation
The presence for the second analyte that object is captured and/or concentration.
Detect the transmitting of the different sections from an optical fiber
In certain embodiments, used the optical fiber for including multiple (such as discontinuous) different pieces along length, such as with
On about any one of optical fiber described in Fig. 5 carry out multiplexing detection.Multiple detectors can be along the length pair of optical fiber
Standard is diacritically to detect the transmitting light from each different piece of the optical fiber.
The multiplexing detection of III.D combinations
In certain embodiments, the different emission of (i) different acceptor dye compositions will be based on；(ii) different donors
The different excitation wavelengths of dye composite；And the multiplexing of different spaces positioning of (iii) the different optical fiber in fiber optic bundle
Method is combined.
For example, different acceptor dye compositions and the combination of donor dye composition can be used to realize a variety of analyses
The multiplexing of object detects.Exactly, in certain embodiments, multiple (such as two) optical fiber in fiber optic bundle are doped with phase
Same acceptor dye composition, but in view of each optical fiber there are different optical fiber to be coupled to its inner surface in conjunction with collocation object and be used to detect
The presence of different analytes and/or concentration.Although the optical fiber doped with same receptor dye composite will be generated with identical hair
The transmitting light of ejected wave length, but based on the excitation wavelength of different donor dye compositions difference, can use doped with different donors
The different donor beads of dye composite distinguish different optical fiber, and therefore distinguish different analytes.
Exactly, in certain embodiments, the first optical fiber in fiber optic bundle and the second optical fiber are doped with common receptor
Dye composite, the acceptor dye composition are different from the acceptor dye combination that all other optical fiber is adulterated in fiber optic bundle
Object.There is first optical fiber the first optical fiber for capturing the first analyte collocation object to be combined to be coupled to its inner surface, and the second optical fiber
Collocation object is combined to be coupled to its inner surface with the second optical fiber for capturing the second analyte.First kind donor bead is doped with tool
There is the first donor dye composition of the first excitation wavelength, and is coated with the first particle combination collocation for being bound to the first analyte
Object.Second Type donor bead is coated with and is bound to doped with the second donor dye composition with the second excitation wavelength
Second particle of the second analyte combines collocation object.Therefore, in the presence of the first analyte, first kind donor bead is adjacent to
The inner surface of one optical fiber, and in the presence of the second analyte, inner surface of the Second Type donor bead adjacent to the second optical fiber.
First kind donor bead is excited with the exciting light irradiation with the first excitation wavelength, and makes the first fibre optical transmission
Light thereby indicates that presence and/or the concentration of the first analyte.With exciting light irradiation the second class of excitation with the second excitation wavelength
Type donor bead, and make the second fibre optical transmission light, thereby indicate that presence and/or the concentration of the second analyte.Therefore, it is based on transmitting
It is in response to generate in which kind of excitation wavelength, the transmitting from first and second optical fiber can be distinguished.Due to the first and second optical fiber
The acceptor dye composition of doping is different from the acceptor dye composition that other optical fiber are adulterated in fiber optic bundle, therefore as retouched above
It states, the transmitting from the first and second optical fiber can be different from the transmitting of other optical fiber in fiber optic bundle by its wavelength.
By this method, in some embodiments it is possible to be combined using the N kind acceptor dyes with N kind distinct emission wavelength
The combination of object and the M kind donor dye compositions with M kind uniqueness excitation wavelengths is examined by the fiber optic bundle comprising N × M optical fiber
Survey N × M kind analytes.In some embodiments it is possible to using the method, but utilize the optical fiber of doping donor dye and doping
The bead of acceptor dye.
IV. sampling method
In certain embodiments, in order to detect the presence of analyte and/or concentration in sample, make optical fiber and/or fiber optic bundle
Contacted with the sample solution comprising detected sample and detection mixture (such as optical fiber and/or fiber optic bundle are immersed into sample solution
In).Detection mixture is the solution comprising donor bead and/or acceptor bead.In certain embodiments, detection mixture includes
The donor bead and/or acceptor bead of one or more types.Each donor bead type and/or acceptor bead type have corresponding
Particle combines collocation object to be coupled to its surface, and the particle combines collocation object to combine specific corresponding analyte of interest.If
Specific analyte of interest is present in sample, then the bead (such as acceptor bead, such as donor bead) of respective type is logical
Crossing corresponding particle combines collocation object to be bound to specific analyte.When by optical fiber (such as immerse sample solution in single optical fiber or
Optical fiber in fiber optic bundle) when immersing in sample solution, the bead that is bound to analyte of interest, which is inhaled into, (such as passes through capillary
Power) optical fiber inside in.If there is optical fiber the corresponding optical fiber for being bound to analyte of interest collocation object to be combined to be coupled in it
Surface, then making the inner surface for the bead adjacent fiber for being bound to analyte of interest.
If bead is doped with donor dye composition donor bead, and optical fiber is doped with acceptor dye composition,
So when being irradiated with exciting light, the donor dye composition that donor bead is adulterated is excited, and by optical fiber adulterated by
Body dye composite launches transmitting light.If bead is acceptor bead and the optical fiber doping doped with acceptor dye composition
There is donor dye composition, then when being irradiated with exciting light, the donor dye composition that optical fiber is adulterated is excited, and pearl
The acceptor dye composition that grain is adulterated launches transmitting light.
In certain embodiments, sample is the fluid sample mixed with detection mixture.In certain embodiments, sample is
The solid sample in solution is crushed and/or be dissolved in, and includes the solution and detection mixture of the sample of crushing and/or dissolving
Mixing.
Figure 14 be describe for collecting sample 1420, prepare sample solution and be introduced into polymer optical fiber beam, and
The signal from polymer optical fiber is read to detect and/or the exemplary method 1400 of one or more quantitative analyte of interest
Figure.In certain embodiments, in sample collection step 1420, by sample 1422 introduce (1426) reaction vessel 1424 (such as
Test tube) in.In sample preparation steps 1440, sample is made to homogenize 1442.For example, solid sample (such as seed) is pressed
It is broken and be mixed in solution.In a further step, the detection mixture 1448 comprising receptor and/or donor bead is added to molten
In liquid (1444) so that sample solution includes sample to be analysed and detection mixture.In a further step, make sample solution and gather
Conjunction object fiber optic bundle (such as the polymer optical fiber beam 300 doped with acceptor dye composition, such as doped with donor dye composition
Polymer optical fiber beam 400) contact 1446, it is (such as logical so that sample solution to be introduced to the inside of polymer optical fiber of fiber optic bundle
Cross capillarity).In certain embodiments, make sample solution in a similar manner with single polymers optical fiber contact, so as to will
Sample solution is introduced into the inside of polymer optical fiber.
Finally, in sample analysis step 1460, polymer optical fiber beam is irradiated with exciting light, and detect resulting hair
It penetrates the presence to detect one or more analyte of interest and/or one or more described analytes is quantified.Such as herein for example
Described in Section III part, the different emission of (i) different acceptor dye compositions is utilized；(ii) different donor dyes
The different excitation wavelengths of composition；And the multichannel multiplexing method of different spaces positioning of (iii) the different optical fiber in fiber optic bundle
It can be used for detecting and/or quantify a variety of analyte of interest.
In the example of Figure 14, fiber optic bundle is loaded into the chuck comprising multiple fiber optic bundles 1462.Chuck 1462 is filled
It carries in (1464) to reader 1462 to detect the signal of one or more fiber optic bundles from the chuck.By being shone with exciting light
It penetrates fiber optic bundle and detects resulting transmitting light using systems and methods described herein, each fiber optic bundle can be read
1466.In certain embodiments, multiple fiber optic bundles of the chuck is made respectively to be contacted with sample solution, and for detect and/or
Quantitative different corresponding analyte of interest.In certain embodiments, make multiple fiber optic bundles of the chuck respectively with comprising not
Different sample solutions with sample contact, and are achieved in the detection of the multiplexing to the multiple analytes from multiple samples.
V. example
Example 1- prepares europium chelating agent Eu (NTA)3BINAPO
Example 1 is an example of the method for being used to prepare the fluorescent chemicals used in acceptor dye composition.At this
In example, compound is europium chelating agent, is exactly Eu (NTA)3BINAPO.Other types of europium chelating agent can also be used
As acceptor dye.In exemplary method, in 50mL round-bottomed flasks, by NTA (4,4,4,-three fluoro- 1- (2- naphthalenes) -1,3-
Diacetyl) (800mg, 3.0mmol) and six chloride hydrate europiums (III) (366mg, 1.0mmol) are dissolved in 10mL straight alcohols together
And to generate europium-NTA solution in triethylamine (700 μ L, 5mmol).Europium-NTA solution is set to be warming up to 75 DEG C in oil bath, simultaneously
Stirring five minutes.([1,1'- binaphthalene] -2,2'- diyls bis- (diphenyl phosphine oxides) (655mg, 1.0mmol) are logical by BINAPO
It crosses and is heated to 75 DEG C and is dissolved in 10mL straight alcohols.Then before cooling (for example, when temperature is still substantially near 75 DEG C
When), solution of the BINAPO of heating in ethyl alcohol is added in europium-NTA solution.That make merging includes europium, NTA and BINAPO
Solution flow back 1 hour, then allow to cool to room temperature.Gained precipitation is collected on filter paper (Hitman 3 (Whatman 3)),
It is washed and is dried under vacuum with ethyl alcohol, it includes Eu (NTA) to obtain 1.28g (80%)3The powder (being in canescence) of BINAPO.
Example 2- prepares Eu (NTA)3BINAPO/C28 oxathiene solution is used to dye hollow polymer optical fiber
Example 2 is the side for being used to prepare the acceptor dye solution comprising chemiluminescence singlet oxygen receptor and fluorescent chemicals
One example of method.Using the acceptor dye solution, with acceptor dye composition (such as comprising chemiluminescence singlet oxygen by
Body and fluorescent chemicals) acceptor dye composition adulterate hollow core polymer optical fiber.In this example, acceptor dye solution packet
The Eu of chelating agent containing europium (NTA)3BINAPO and C28 oxathienes.C28 oxathienes be chemiluminescence singlet oxygen by
Body and europium chelating agent is fluorescent chemicals.In this example, Eu (NTA)3BINAPO (160mg, 0.10mmol) passes through heating
It is dissolved in the cellosolvo of 3.2mL to 70 DEG C and reaches 50mg/mL ultimate densities.C28 oxathienes (4- (2-
Phenyl -5,6- dihydro-Isosorbide-5-Nitrae-thioxane -3- bases)-N, the bis- myristyl aniline of N-) (80mg, 0.12mmol) by adding
Heat is dissolved in the cellosolvo of 3.2mL to 70 DEG C and reaches 25mg/mL ultimate densities.Merge two kinds of solution, keeps its cold
But it to room temperature (20 DEG C), is then filtered by 0.7 μ glass microfibers syringe filter (Hitman).It will be filtered final molten
Liquid is stored in dark place and uses (such as doped polymer optical fibers) in twenty four hours.
Example 3- is used to increase the porous hollow polymer optical fiber of combined surface area
Example 3 is one of the multicore hollow polymer optical fiber comprising multiple hollow cores (such as hollow channel in optical fiber)
A example.Multicore hollow polymer optical fiber makes the surface area combined for analyte increase, and makes analyte or analytical reagent
Reach the Distance Shortened spread needed for hollow polymer optical fiber surface.Figure 15 is the image of multicore hollow polymer optical fiber.Figure 15 B
It is another image of multicore hollow polymer optical fiber.Figure 15 C are the multiple hollow cores for showing multicore hollow polymer optical fiber
The image of fiber end face.
Multicore hollow polymer optical fiber in this example is made of polystyrene, has 1.3mm outer diameters and includes 19
Internal diameter is 105 μm of hollow channel, these hollow channels respectively (such as include chemiluminescence with acceptor dye composition simultaneously
Object is closed, such as includes chemiluminescence singlet oxygen receptor and fluorescent chemicals) dyeing.
Example 4- prepares hollow polymer optical fiber to be dyed to its inner surface with acceptor dye composition
Example 4 is to be used to prepare hollow polymer optical fiber so that the side of optical fiber doping receptor and/or donor dye composition
One example of method and system component.It, will in order to use receptor and/or donor dye composition doped fiber in exemplary method
Polymer optical fiber is connected to syringe.Using syringe by the solution comprising acceptor dye and/or donor dye composition, and
Solution (such as water, ethyl alcohol) for cleaning inside of optical fibre is pumped in optical fiber.Polymer optical fiber passes through appropriately sized screw thread
Pipe fitting nut and casing connection are to syringe.For the polymer optical fiber of 1.3mm, 1/16 inch of efficient (height can be used
Pressure) liquid chromatogram (HPLC) connector.Collar nut is attached to coupler, coupler and is attached to syringe or syringe pump.
Figure 16 shows two images of one section of hollow polymer optical fiber for being attached to connector (left-side images) and syringe (image right).
Example 5- adulterates the inside of hollow polymer optical fiber with acceptor dye composition
Example 5 is adulterated with acceptor dye composition (such as comprising chemiluminescence singlet oxygen receptor and fluorescent chemicals)
One example of the method for the inside of one section of hollow polymer optical fiber.In exemplary method, acceptor dye composition includes C28 oxygen
Thia cyclohexene and europium chelating agent (Eu (NTA)3BINAPO)。
The Eu (NTA) that will be prepared as described in above example 23BINAPO and C28 oxathienes are in 2- ethyoxyls
A part (600 μ L) in acceptor dye solution in ethyl alcohol is put into test tube and is heated to 70 DEG C in oil bath.In order to adulterate
The inside of hollow polymer optical fiber, the 19 holes polymerization by the hollow polymer optical fiber of 15cm length, such as described in above example 3
Object light fibre is attached to the syringe as described in above example 4.Syringe is filled with the ethyl alcohol of 200 proofs.It pushes
Ethyl alcohol passes through the hollow polymer optical fiber of attachment, thus contacts it and soaks the inner surface of optic fibre hole.Then using dry note
Emitter, with air douche optical fiber.Then, the Eu after heating (NTA)3BINAPO and C28 oxathienes are in 2- ethyoxyl second
Dye solution in alcohol is rapidly and fully sucked in optical fiber in (such as in multiple holes of sucking porous hollow polymer optical fiber).
Apparent fluorescence is presented under long wavelength's UV excitations (about 366nm, hand-held lamp) in the optical fiber of whole length, determines optical fiber
The presence of inner recipient dye solution.The optical fiber of other length is attached to syringe and is dyed in the same manner.It can also pass through
Exemplary method carries out part doping to optical fiber.Exactly, dye solution can be sucked away from optical fiber end specific range (example
Such as relatively short distance, such as 1 to 2cm) in selected fiber section in.By making away from the selected light in optical fiber end specific range
Fine part is contacted with acceptor dye, can adulterate selected fiber section, and the rest part of optical fiber can keep undoped.
The optical fiber that will be filled with dye solution is put into baking oven, is kept at 80 DEG C about 5 minutes, is then taken out and keep its cold
But to room temperature, and 20 minutes are stood at room temperature.Optical fiber is attached to syringe and is removed by forcing air across again
Dye solution, then sequentially with the ethyl alcohol of 200 proofs, empty gas and water and air cleaning in dry optical fiber capillary
Portion.
Example 6- carrys out the transmitting of the hollow polymer optical fiber of auto-dope acceptor dye and along the hollow of doping acceptor dye
The characterization of the optical transport of polymer optical fiber
Example 6 is shown in fluorescent chemicals (such as europium chelating agent) that auto-dope is useful in acceptor dye composition
One example of the characterization of the light of empty polymer optical fiber transmitting.This example also shows the characterization of the optical transport along optical fiber.At this
In example, the optical fiber of europium doped chelating agent is prepared as described in above example 5.As described in above example 5, filled out in optical fiber
Acceptor dye solution, heating and after cooling down are filled, optical fiber is attached to syringe again and by forcing air across optical fiber come clear
Except dye solution.Then optical fiber is cleaned with the ethyl alcohol of 200 proofs, forces air across optical fiber again later.Finally, it uses
Water cleans optical fiber, and forces air across optical fiber again with the inside of dry optical fiber capillary.
Pass through hand-held laboratory UV lamp, the ultraviolet light optical fiber for being 366nm with wavelength.Optical fiber can be observed to be mixed
The presence of europium chelate dyes in miscellaneous europium chelating agent transmitting fluorescence and determining optical fiber.Figure 17 A are the optical fiber of europium doped chelating agent
1702 image, described image show the fluorescent emission of the optical fiber caused by ultraviolet light.
Figure 17 B and Figure 17 C are the images of different optical fiber.Only in the end 1 away from optical fiber shown in Figure 17 B and Figure 17 C to 2cm
Interior a part of optical fiber europium doped chelate dyes, and be not incorporated in optical fiber other parts dyestuff (optical fiber rest part without
Overdoping).Figure 17 B are the images of the optical fiber end through overdoping, show the transmitting for the europium chelating agent that end is adulterated from optical fiber.Figure
17C is the image of the other end without overdoping of optical fiber.Figure 17 C, which are shown, leaves optical fiber undoped with end by ultraviolet excitation
The light that the doping end of optical fiber generates (undoped with the unused ultraviolet light in end shown in Figure 17 C).Optical transport of the optical fiber undoped with end
It shows that europium chelating agent emits from the doping end of optical fiber, transmits along polymer optical fiber and left from the optical fiber other end.
Characterization of polymer optical fibers of the example 7- through overdoping to the response of singlet oxygen
Example 7 is display doped with the receptor of singlet oxygen containing chemiluminescence (such as oxathiene, such as C28 oxygen sulphur
Heterocycle hexene) and fluorescent chemicals (such as europium chelating agent) acceptor dye composition polymer optical fiber in response to singlet oxygen
An and example of the photoemissive characterization generated.Test polymer optical fiber is doped with including europium chelating agent and C28- oxygen thia rings
The acceptor dye composition of hexene.
It, will about 2.5mm length in order to test the transmitting for coming from test optical fiber (europium doped chelating agent and oxathiene)
A bit of test optical fiber be put into the hole of 384 orifice plates.Using undoped polymer optical fiber as the first control fiber.By portion
The first control fiber (undoped optical fiber) is divided to be put into another hole of 384 orifice plates.Europium chelating agent (and not oxygen-containing sulphur will only be used
Heterocycle hexene) dyeing optical fiber be used as the second control fiber.By the second control fiber of part (only europium doped chelating agent and not oxygen-containing
Thia cyclohexene) it is put into the third hole of 384 orifice plates.
Figure 18 A are that three kinds of different optical fiber (test optical fiber, the first control fiber and the second control fiber) are each in display orifice plate
The image (1820) of transmitting of the section under the irradiation of 366nm length ultraviolet lines.Undoped first control fiber 1822 emits indigo plant
Color fluorescence.The blue-fluorescence emitted by the first control fiber is manufacture optical fiber (test optical fiber, the first control fiber and the second control
Optical fiber) polystyrene intrinsic fluorescence.Test optical fiber 1824 (europium doped chelating agent and C-28 oxathienes) and second
Control fiber 1826 (only europium doped chelating agent and be free of oxathiene) emits red fluorescence, and this fluorescence is by optical fiber
The fluorescence of the 1824 and 1826 europium chelating agents adulterated generates.
Next, 384 orifice plates for being placed with optical fiber are put into EnVision multiple labeling plate readers (EnVision
Multilabel Reader) (PerkinElmer (PerkinElmer, Waltham, MA) of Massachusetts Waltham) simultaneously
In narrowband europium optical filter (such as to wavelength correspond to europium emit light wavelength light substantial transparent and to other wavelength
Light is substantially non-transparent optical filter) in the presence of read with light-emitting mode.In the presence of no excitaton source, test optical fiber, first pair
Any of irradiation fibre and the second control fiber are not all observed luminous.
Then, by being immersed in different optical fiber comprising sodium molybdate and hydrogen peroxide in deuterium oxide (D2O in the solution in),
These optical fiber are stimulated with singlet oxygen.It is not fettered by specific theory, molecular oxygen is converted to due to hydrogen peroxide catalyzed, therefore sodium molybdate
With hydrogen peroxide in D2Solution (hereinafter referred to as " MoO in O4 -2/H2O2Solution ") through a period of time generate the list of Css
Line state oxygen.D2O be used to extend the service life of resulting singlet oxygen.By MoO4 -2/H2O2The singlet oxygen that solution generates
Intensity is suitable with the expected intensity excited by photosensitizer.By MoO4 -2/H2O2The intensity for the singlet oxygen that solution generates is enough to make list
Line state oxygen reactive reagent, as AlphaLISA acceptor beads generate measurable light output.
MoO4 -2/H2O2Solution prepares as follows.Prepare includes 1mM sodium molybdates, 10mM potassium carbonate and 0.2% Tween-20
(Tween-20) detergent is in D2Molybdate solution in O.Prepare the D containing 3% hydrogen peroxide2O.Immediately before use by molybdic acid
Salting liquid (450 μ L) is combined with hydrogenperoxide steam generator (50 μ L).This solution will persistently generate singlet oxygen within a few hours.
It will the different optical fiber in part, i.e. test optical fiber, the first control fiber and the second control fiber immersion MoO4 -2/H2O2Solution
In.It is not fettered by specific theory, immerses MoO when optical fiber (doped with C28 oxathienes and europium chelating agent) will be tested4 -2/
H2O2When in solution, by MoO4 -2/H2O2Solution generate stable state singlet oxygen (1O2) with the chemiluminescence adulterated of test optical fiber
Singlet oxygen receptor (such as C28 oxathienes) reacts.C28 oxathienes are reacted with singlet oxygen generates ultraviolet light
Thus transmitting excites europium chelating agent, europium chelating agent then to emit fluorescence.Therefore, when being put into MoO4 -2/H2O2When in solution, from mixing
The test optical fiber of two kinds of miscellaneous europium chelating agent and C-28 oxathienes detects high RST (1000 times higher than background).
When by undoped first control fiber immerse MoO4 -2/H2O2When in solution, from undoped first control fiber
It detects and the comparable signal of background signal.Similarly, when by the second control fiber (only europium doped chelating agent and not oxygen-containing thia
Cyclohexene) immerse MoO4 -2/H2O2When in solution, detect and the comparable signal of background signal.
Figure 18 B are shown comprising by imagining multiple labeling reader (PerkinElmer of Massachusetts Waltham) record
The data for corresponding to the signal detected from test optical fiber, the first control fiber and the second control fiber screenshotss 1840.It cuts
Screen is shown in the first control fiber position 1842, test fiber position 1844 and the second control fiber position in porous plate
1846.Number in figure at each fiber position corresponds to the amplitude for the signal that each fiber position detects from plate (to count
Measurement).Exactly, it detects signal 106,360 from test optical fiber, and is detected from the first and second control fibers much smaller
Signal, respectively 60 and 80.
Figure 18 C, which are shown, is depicted in MoO4/H2O2Under stimulation from three kinds of fiber laser arrays to signal Figure 188 0.Figure
18 figure also shows background signal (such as without any MoO4/H2O2Detected signal when stimulation).Control fiber exists
MoO4/H2O2The lower signal generated of stimulation is suitable with background signal, and the survey of europium doped chelating agent and oxathiene compound
Optical fiber is tried in MoO4/H2O2The lower signal 1886 generated of stimulation is apparently higher than background signal (such as 1,000 times high).
Therefore, example 7 illustrates the transmitting generated by singlet oxygen channel doped with the optical fiber of acceptor compound.
The streptavidin coating of example 8- chemiluminescence polymer optical fibers
Example 8 is the inner surface doped with the polymer optical fiber of acceptor dye composition with streptavidin coating
One example of method.Streptavidin may be used as optical fiber combine collocation object (such as be bound to biotinylation analysis
Object) or as optical fiber combine the coating that collocation object can be attached (such as biotinylated antibody can be bound to avidin chain bacterium
Element coating).In the exemplary method of example 8, the obtained streptavidin in lyophilized solid form is dissolved in packet
Na containing 100mM2HPO4In the coating buffer of/50mM citric acids pH 5.0, reach 5 to 25 μ g/mL ultimate densities.By antibiosis egg
In white streptavidin solution inhalation syringe and one section 15 is pumped across to 50cm through overdoping (such as doped with receptor combination object)
Polymer optical fiber capillary.Then parafilm hermetic fiber end is used.In insulating box containing moisture, light is incubated at 37 DEG C
It is 24 hours fine.Then with DELFIA board-washings machine (the Perkin Ai Er of Massachusetts Waltham comprising 0.05% Tween-20
It is silent) rinse optical fiber.Then with 0.2% bovine serum albumin(BSA) (BSA) and 6%D- D-sorbites in 50mM Tris-HCl (pH
7.0), the solution in 150mM NaCl fills (such as passing through the syringe as described in above example 4) optical fiber.Use parafilm
The end of hermetic fiber is simultaneously stored in insulating box, is kept overnight at 23 DEG C.It, will by the way that air is conveyed through optical fiber
BSA solution removals go out optical fiber.Then by the way that drying nitrogen is conveyed through optical fiber 10 minutes come dry optical fiber.
Sensitiser dye is embedded in the inside of one section of hollow polymer optical fiber by example 9-
Example 9 is the one of the method for the inside for donor dye (such as photosensitizer) to be embedded in hollow polymer optical fiber
A example.For example, hollow polymer optical fiber can be doped with the donor dye composition comprising naphthalene phthalocyanine.In this example
In, by bis- (three hexyl silane base oxygen) silicon (20mg, 15 μm of ol of 2,3- naphthalene phthalocyanines；Sigma Aldrich
(SigmaAldrich) 389935) be put into vial, and by be heated to about 100 DEG C and apply be ultrasonically treated its is molten
Solution is in 4mL cellosolvos.A part (600 μ L) for this solution is put into test tube and is heated to 80 DEG C in oil bath.
As described in example 4, the hollow polymer optical fiber of 15cm length is attached to syringe.Syringe is filled with 200 standard wine
The ethyl alcohol of precision and push ethyl alcohol pass through attachment hollow polymer optical fiber to soak the inner surface of optical fiber capillaries.Then make
With dry injection device, with air douche optical fiber.Then the sensitiser dye solution of warm is rapidly and fully sucked into polymer
In optical fiber.
The optical fiber that will be filled with dye solution is put into baking oven, is kept at 80 DEG C about 5 minutes, is then taken out and keep its cold
But to room temperature.Optical fiber is kept 20 minutes at room temperature.Optical fiber is attached to syringe and is removed by forcing air across again
Dye solution, then sequentially with the ethyl alcohol of 200 proofs, empty gas and water and air cleaning in dry optical fiber capillary
Portion.In the dark by the storage of obtained sensitizer polymer optical fiber.
The streptavidin coating of example 10- donor polymerizations object light fibre
Example 10 be with streptavidin be coated with doping donor dye (such as photosensitizer) polymer optical fiber it is interior
One example of the method in portion.The obtained streptavidin in lyophilized solid form is dissolved in comprising 100mM
Na2HPO4In the coating buffer of/50mM citric acids (pH 5.0), reach the ultimate density of 5 to 25 μ g/mL.By avidin chain
Be pumped across in rhzomorph solution inhalation syringe and under soft illumination condition (such as in low-level ambient light) one section 15 to
The capillary of the doping donor dye polymer optical fiber of 50cm.Then parafilm hermetic fiber end is used.In insulating box containing moisture
In, incubate optical fiber in the dark at 37 DEG C 24 hours.Then with the DELFIA board-washing machines (Ma Sazhu comprising 0.05% Tween-20
Fill in the PerkinElmer of state Waltham) rinse optical fiber.Then with 0.2% bovine serum albumin(BSA) (BSA) and 6%D- D-sorbites
Solution in 50mM Tris-HCl (pH 7.0), 150mM NaCl fills (such as passing through syringe) optical fiber.It is close with parafilm
The end of optical fiber is sealed, and by fiber optic storage in insulating box.It is kept overnight in dark place at 23 DEG C.After incubation, by will be empty
Gas is conveyed through optical fiber and BSA solution removals is gone out optical fiber.Then, by making drying nitrogen across optical fiber 10 minutes come dry optical fiber
And it stores in the dark.
VI. network environment and computing system
As shown in Figure 19, it shows and describes for providing retrieval, processing and analyzing via described herein hollow
Network environment in the systems of the data that polymer optical fiber system (such as via customization diagnostic software) generates, method and framework
1900 embodiment.Simply, referring now to Figure 19, show and describe the block diagram of exemplary cloud computing environment 1900.Cloud
Computing environment 1900 may include one or more resource providers 1902a, 1902b, 1902c (being referred to as 1902).Each resource
Supplier 1902 may include computing resource.In some embodiments, computing resource may include handling appointing for data
What hardware and/or software.For example, computing resource may include being able to carry out algorithm, computer program and/or computer to answer
With the hardware and/or software of program.In some embodiments, example calculation resource may include with storage and retrieval energy
The apps server and/or database of power.Each resource provider 1902 can be connected in cloud computing environment 1900
Any other resource provider 1902.In some embodiments, resource provider 1902 can connect through computer network 1908
It connects.Each resource provider 1902 can be connected to through computer network 1908 one or more computing devices 1904a, 1904b,
1904c (is referred to as 1904).
Cloud computing environment 1900 may include explorer 1906.Explorer 1906 can be through computer network
1908 are connected to resource provider 1902 and computing device 1904.In some embodiments, explorer 1906 can promote
Computing resource is provided in one or more computing devices 1904 into one or more resource providers 1902.Explorer 1906
The request of the related computing resource from particular computing device 1904 can be received.Explorer 1906, which can differentiate, to be carried
For one or more resource providers 1902 of the computing resource required by computing device 1904.Explorer 1906 can select
Resource provider 1902 is to provide computing resource.Explorer 1906 can promote resource provider 1902 to be filled with specific calculation
Set the connection between 1904.In some embodiments, explorer 1906 can establish specific resources supplier 1902 with
Connection between particular computing device 1904.In some embodiments, explorer 1906 can be by particular computing device
1904 are redirected the specific resources supplier 1902 with required computing resource.
Figure 20 shows the computing device 2000 and mobile computing device that can be used for implementing the technology described in the disclosure
2050 example.The intention of computing device 2000 represents various forms of digital computers, such as laptop computer, desktop
Computer, work station, personal digital assistant, server, blade server, mainframe computer and other suitable computers.It is mobile
Computing device 2050 intention represent various forms of mobile devices, as personal digital assistant, cellular phone, smart phone and its
It is similar to computing device.Component, its connection and relationship shown here and its function are meant only as example, without being intended for
For limitation.
Computing device 2000 includes processor 2002, memory 2004, storage device 2006, is connected to 2004 and of memory
The high-speed interface 2008 of multiple high-speed expansion ports 2010, and it is connected to the low of low-speed expansion port 2014 and storage device 2006
Quick access mouth 2012.Processor 2002, memory 2004, storage device 2006, high-speed interface 2008, high-speed expansion ports 2010 and
Low-speed interface 2012 respectively uses various bus interconnections, and may be mounted in common motherboard or pacify in other ways when appropriate
Dress.Processor 2002 can handle for executing in the computing device 2000 instruction (including be stored in memory 2004 or
Instruction on storage device 2006) at external input/output device (display 2016 for being such as coupled to high-speed interface 2008)
Upper display GUI graphical informations.In other embodiments, multiple processors and/or multiple buses can be used on demand, and
Multiple memories and type of memory.In addition, multiple computing devices can link together, wherein each device provides necessary behaviour
The part (such as server group, one group of blade server or multicomputer system) of work.
Memory 2004 stores information in computing device 2000.In some embodiments, memory 2004 is one
Or multiple volatile memory-elements.In some embodiments, memory 2004 is one or more nonvolatile memory lists
Member.Memory 2004 can also be another form of computer-readable media, such as disk or CD.
Storage device 2006 can be that computing device 2000 provides mass memory.In some embodiments, storage device
2006 can be or contain computer-readable media, such as diskette unit, hard disk device, optical disc apparatus or magnetic tape equipment, flash memory
Reservoir or other similar solid-state storage devices or apparatus array, the device being included in storage area network or other configurations.
Instruction can be stored in information carrier.Described instruction when being executed by one or more processing units (such as processor 2002) into
One or more methods of row, those methods as described above.Instruction can also be stored by one or more storage devices, such as be calculated
Machine or machine-readable medium (such as memory 2004, storage device 2006 or memory on processor 2002).
High-speed interface 2008 manages the bandwidth-intensive operations of computing device 2000, and low-speed interface 2012 manages lower bandwidth
Intensive action.This function distribution is an example.In some embodiments, high-speed interface 2008 is coupled to memory
2004, display 2016 (such as passing through graphics processor or accelerator) and high-speed expansion ports 2010 are coupled to, the high speed
ECP Extended Capabilities Port can receive various expansion card (not shown).In the embodiment described in which, low-speed interface 2012 is coupled to storage dress
Set 2006 and low-speed expansion port 2014.Including various communication port (such as USB,Ethernet
(Ethernet), wireless ethernet) low-speed expansion port 2014 can be coupled to one or more input/output devices, such as key
Disk, indicator device, scanner or interconnection device such as exchanger or router, such as networked by network interface card.
As shown in the figure, computing device 2000 can be implemented by many different forms.For example, it can be taken by standard
The form of business device 2020 is implemented, or repeatedly implements in one group of such server.In addition, it can be in personal computer as taken down notes
Implement in this computer 2022.It is also used as a part for frame server system 2024 and implements.Alternatively, computing device 2000
Component can with mobile device (not shown), such as in mobile computing device 2050 other components combination.These devices are respectively
Can be containing one or more in computing device 2000 and mobile computing device 2050, and holonomic system can be by communicating with one another
Multiple computing devices constitute.
Mobile computing device 2050 include processor 2052, memory 2064, input/output device such as display 2054,
Other components such as communication interface 2066 and transceiver 2068.Mobile computing device 2050 can also have storage device, such as miniature
Driver or other devices, to provide extra storage.Processor 2052, memory 2064, display 2054, communication interface 2066
And transceiver 2068 is individually to use various bus interconnections, and several in these components may be mounted in common motherboard
Or it is installed in other ways when appropriate.
Processor 2052 can execute the instruction in mobile computing device 2050, including the finger being stored in memory 2064
It enables.Processor 2052 can be implemented by the chipset form formed by chip, and the chip includes independent multiple simulation sum numbers
Word processing device.Processor 2052 can for example realize mobile computing device 2050 other components (control of such as user interface),
The coordination of the wireless communication of the application program and mobile computing devices 2050 that run by mobile computing device 2050.
Processor 2052 can be by being coupled to control interface 2058 and display interface 2056 and the user of display 2054
Communication.Display 2054 can be such as TFT (Thin Film Transistor-LCD) displays or OLED (organic light-emitting diodes
Pipe) display or other display technologies appropriate.Display interface 2056 can include for drive display 2054 with to
The proper circuit of figure and other information is presented in family.Control interface 2058 can from user receive order and it is converted with
Submit to processor 2052.In addition, external interface 2062 can be communicated with processor 2052, to realize mobile computing device
2050 with the near-field communications of other devices.External interface 2062 can for example provide in some embodiments wire communication or
Wireless communication is provided in other embodiments, and multiple interfaces can also be used.
Memory 2064 stores information in mobile computing device 2050.Memory 2064 can be by one or more calculating
One or more in machine readable media, one or more volatile memory-elements or one or more Nonvolatile memery units
Form implement.Extended menory 2074 can also be provided and it is connected to mobile computing device by expansion interface 2072
2050, the expansion interface may include such as SIMM (single-in-line memory module) card interface.Extended menory 2074 can
To provide additional memory space for mobile computing device 2050, or application program or related mobile computing dress can also be stored
Set 2050 other information.Exactly, extended menory 2074 may include related progress or supplement process as described above
Instruction, and can also include security information.Thus, for example, extended menory 2074 can be used as mobile computing device
2050 security module provides, and can program and have the instruction for allowing to use mobile computing device 2050 safely.In addition,
Security application and additional information can be provided by SIMM cards, such as by can not by hacker attack in a manner of by identification information
It is placed on SIMM cards.
Memory may include such as flash memory and/or NVRAM memory (nonvolatile RAM),
As discussed below.In some embodiments, instruction is stored in information carrier.Described instruction is by one or more processing
Device (such as processor 2052) carries out one or more methods when executing, those methods as described above.Instruction can also
It is stored by one or more storage devices, such as one or more computers or machine-readable medium (such as memory 2064, extension storage
Memory on device 2074 or processor 2052).In some embodiments, instruction can be for example through transceiver 2068 or outer
Portion's interface 2062 receives in the signal of propagation.
Mobile computing device 2050 can be wirelessly communicated by communication interface 2066, and when necessary, the communication interface can be with
Including digital signal processing circuit.Communication interface 2066 can provide the communication according to various patterns or agreement, as GSM speeches are exhaled
It is (global system for mobile communications), SMS (short message service), EMS (Enhanced Messaging Service) or MMS message sending and receiving (more matchmakers
Body information service), CDMA (CDMA access), TDMA (time division multiple acess access), PDC (personal digital cellular), WCDMA it is (wide
Band CDMA accesses), CDMA2000 or GPRS (General Packet Radio Service) etc..Such communication can be for example using penetrating
Frequently, occurred by transceiver 2068.In addition, short range communication can for example usingWiFiTMOr other such transmitting-receivings
Device (not shown) and occur.In addition, GPS (global positioning system) receiver module 2070 can be carried to mobile computing device 2050
For additional navigation wireless data related to position, what the data can be run on mobile computing device 2050 in due course
Application program uses.
Mobile computing device 2050 can also be communicated using audio codec 2060 with audible, and the audio compiles solution
Code device can receive verbal information from the user and be converted into available digital information.Audio codec 2060 is same
Sample can be such as by loud speaker, such as in the hand-held set of mobile computing device 2050.It is such to generate the audible sound of user
Sound may include sounds from voice phone calls, may include sound (such as voice messaging, the music file of record
Deng) and can also include the sound generated by the application program operated on mobile computing device 2050.
As shown in the figure, mobile computing device 2050 can be implemented by many different forms.It for example, can be by bee
2080 form of socket phone is implemented.It can also be used as smart phone 2082, personal digital assistant or other similar mobile devices
A part implement.
The various embodiments of system and technology described herein can in Fundamental Digital Circuit, integrated circuit, specially set
It is realized in the ASIC (application-specific integrated circuit) of meter, computer hardware, firmware, software and/or a combination thereof.The various embodiments
May include the embodiment in one or more computer programs, the computer program can execute on programmable systems and/
Or interpretation, the programmable system includes at least one programmable processor, it can be it is dedicated or general, through couple with
Receive data and instruction from storage system, at least one input unit and at least one output device, and to storage system,
At least one input unit and at least one output device transmission data and instruction.
These computer programs (also referred to as program, software, software application or code) include for programmable processing
The machine instruction of device, and the programming language of advanced procedures and/or goal orientation can be used and/or with compilation/machine language reality
It applies.As used herein, term machine-readable medium and computer-readable media refer to for putting forward machine instruction and/or data
It is supplied to any computer program product of programmable processor, equipment and/or device (such as disk, CD, memory, can be compiled
Journey logic device (PLD)), including receive the machine-readable medium of the machine instruction of machine-readable signal form.Term machine can
Read signal refers to machine instruction and/or data to be supplied to any signal of programmable processor.
In order to realize that the interaction with user, system and technology described herein can be implemented on computers, the calculating
Equipment is useful for showing the display device of information (for example, CRT (cathode-ray tube) or LCD (liquid crystal display) monitoring to user
Device) and user can be used to computer provide input keyboard and indicator device (such as mouse or trace ball).Other types
Device can be equally used for realizing and the interaction of user；For example, the feedback provided a user can be any type of
Sense feedback (such as visual feedback, audio feedback or touch feedback)；And input from the user can be connect by any form
It receives, including sound equipment, voice or sense of touch.
System and technology described herein can be implemented in computing systems, and the computing system includes aft-end assembly (example
Such as data server), or including middleware component (such as apps server), or including front end assemblies (such as with figure
The client computer of shape user interface or Web browser, user can by graphical user interface or Web browser with herein
The interaction of the embodiment of the system of description and technology) or such rear end, middleware or front end assemblies any combinations.The system
Component can pass through any form or the digital data communications (such as communication network) of media interconnection.The example packet of communication network
Include LAN (LAN), wide area network (WAN) and internet.
Computing system may include client and server.Client and server is generally off-site from each other and usually by logical
Communication network interacts.Client and the relationship of server are by means of being run on computer out of the ordinary and having client-each other
The computer program of relationship server generates.
The element of different embodiments described herein can be combined to form the other implementations not being specifically described above
Scheme.Element can be omitted from approach described herein, computer program, database, without negatively affecting its behaviour
Make.In addition, the logic flow described in schema need not reach required knot by shown certain order or sequential order
Fruit.Various independent components can be combined into one or more individual components to execute functionality described herein.In some embodiment party
In case, it is contemplated that structure, function and the equipment of system and method described herein.
By equipment and System describe be have including or comprising specific components, or technique and method is described as having,
In entire description content including or comprising particular step, it is also contemplated that in the presence of being mainly made of the component or by the component
The equipment and system of the present invention of composition, and exist and be mainly made of the processing step or be made of the processing step
Process according to the invention and method.
It should be understood that the order of step or order for executing certain actions are not important, as long as present invention holding can grasp
Work.In addition, two or more steps or action can be carried out at the same time.
Although particularly shown with reference to specific preferred embodiment and describe equipment, system and method, this field
It should be understood to the one skilled in the art that the spirit and scope of the present invention being defined by the following claims can not departed from,
The variation of various forms and details is carried out wherein.
Claims (92)
1. a kind of doped with acceptor dye composition and/or the polymer optical fiber of donor dye composition, the optical fiber can pass
The defeated light generated by singlet oxygen channel is to detect and/or quantify the analyte of interest in sample.
2. polymer optical fiber according to claim 1, wherein polymer optical fiber are doped with acceptor dye composition.
3. polymer optical fiber according to claim 2, wherein the acceptor dye composition includes chemiluminescence singlet
Oxygen acceptor and fluorescent chemicals.
4. polymer optical fiber according to claim 3, wherein the chemiluminescence singlet oxygen receptor is selected from by with the following group
At group：Oxathiene, dioxine and dithia cyclohexene.
5. the polymer optical fiber according to any claim in claim 3 or 4, wherein the fluorescent chemicals are group of the lanthanides
Element chelating agent.
6. polymer optical fiber according to claim 5, wherein the lanthanide series chelating agent includes selected from consisting of
The lanthanide series of group：Europium, terbium, dysprosium, samarium, ytterbium, erbium and thulium.
7. the polymer optical fiber according to any claim in claim 3 or 4, wherein the fluorescent chemicals include
Engine dyeing material.
8. the polymer optical fiber according to any claim in claim 2 to 7, wherein the polymer optical fiber doped with
Quantum dot.
9. polymer optical fiber according to claim 1, wherein the polymer optical fiber is doped with donor dye composition.
10. polymer optical fiber according to claim 9, wherein the donor dye composition includes to work as to be irradiated with exciting light
When discharge singlet oxygen photosensitizer.
11. polymer optical fiber according to claim 10, wherein the photosensitizer is the chemical combination selected from group consisting of
Object：Phthalocyanine, naphthalene phthalocyanine, chlorin, porphines, porphyrin, stellacyanin, chlorophyll and Bengal rose red.
12. the polymer optical fiber according to any claim in claim 1 to 11, wherein the polymer optical fiber has
The internal diameter and 1mm of 0.1mm to 2mm to 3mm outer diameter.
13. the polymer optical fiber according to any claim in claim 1 to 12, wherein the polymer optical fiber is interior
Diameter is 0.5mm to 1.5mm.
14. the polymer optical fiber according to any claim in claim 1 to 13, wherein the polymer optical fiber is interior
Diameter is sufficiently small to be drawn liquid into the inside of the polymer optical fiber by capillarity.
15. the polymer optical fiber according to any claim in claim 1 to 14, wherein the polymer optical fiber has
The internal diameter for keeping capillarity, the inside of the polymer optical fiber is drawn liquid into from there through capillarity.
16. the polymer optical fiber according to any claim in claim 1 to 15, it includes be incorporated into the polymer
First on the inner surface of optical fiber combines collocation object.
17. the polymer optical fiber according to any claim in claim 1 to 16, wherein the polymer optical fiber is along it
Length includes multiple discontinuous parts, and respectively the first combination collocation object with various concentration is coupled to it for the part
Inner surface is to realize the measurement of a variety of level of sensitivity for the analyte of interest for combining collocation object to be combined to described first.
18. the polymer optical fiber according to any claim in claim 1 to 17, wherein the polymer optical fiber is along it
Length includes multiple discontinuous parts, and respectively there is different combinations collocation object to be coupled to its inner surface.
19. polymer optical fiber according to claim 18, wherein the different combination collocation objects are different antibodies.
20. the polymer optical fiber according to any claim in claim 18 or 19, wherein each combine collocation object can
It is bound to the different variants of specific antigen.
21. the polymer optical fiber according to any claim in claim 18 to 20, wherein each combine collocation object can
It is bound to different analytes.
22. the polymer optical fiber according to any claim in claim 1 to 21, wherein the polymer optical fiber includes
Multiple hollow cores.
23. the polymer optical fiber according to any claim in claim 1 to 22, wherein the polymer optical fiber includes
Polystyrene and/or poly- (methyl methacrylate).
24. a kind of polymer optical fiber beam, each optical fiber of the fiber optic bundle is doped with corresponding acceptor dye composition and/or donor
Dye composite.
25. polymer optical fiber beam according to claim 24, wherein the fiber optic bundle includes 2 to 20 polymer optical fibers.
26. the polymer optical fiber beam according to any claim in claim 24 or 25, wherein the fiber optic bundle is more
A polymer optical fiber is respectively doped with unique acceptor dye composition.
27. the polymer optical fiber beam according to any claim in claim 24 to 26, wherein the fiber optic bundle is more
A polymer optical fiber is respectively doped with unique donor dye composition.
28. the polymer optical fiber beam according to any claim in claim 24 to 27, wherein the fiber optic bundle is more
Respectively there is a polymer optical fiber unique combination collocation object to be coupled to its inner surface.
29. a kind of chuck including multiple polymer optical fiber beams, wherein each polymer optical fiber of each fiber optic bundle is doped with phase
Answer acceptor dye composition and/or corresponding donor dye composition.
30. chuck according to claim 29, wherein for each fiber optic bundle of the chuck, the fiber optic bundle it is multiple
Respectively there is the polymer optical fiber unique combination collocation object to be coupled to its inner surface.
31. a kind of system for detecting single analyte and/or multiple analytes, the system include：
Doped with acceptor dye composition and/or the polymer optical fiber of donor dye composition；
Excitation light source；And
Detector for detecting the transmitting light generated by singlet oxygen channel for travelling across the polymer optical fiber.
32. system according to claim 31, wherein the detector leaves the polymer light by alignment to detect
The light of fine end face.
33. the system according to any claim in claim 31 or 32, wherein the detector by being aligned so that
It obtains its zone of action and the axis of the polymer optical fiber is substantially concentric.
34. the system according to any claim in claim 31 to 33, wherein the excitation light source by alignment with
Length along the polymer optical fiber irradiates the polymer optical fiber.
35. the system according to any claim in claim 31 to 33, wherein the excitation light source by alignment with
The polymer optical fiber is being irradiated on the direction of the polymer optical fiber.
36. the system according to any claim in claim 31 to 35, wherein the excitation light source is with substantially
The laser of single wavelength operation.
37. the system according to any claim in claim 31 to 36, additionally comprises shell, wherein：
The shell surrounds the detector and the polymer optical fiber,
The shell includes excitation optical port, and the exciting light from the excitation light source can be guided through the exciting light end
Mouthful, and
The shell is substantially opaque to ambient light.
38. the system according to any claim in claim 31 to 36, additionally comprises shell, wherein：
The shell surrounds the detector, the polymer optical fiber and the excitation light source, and
The shell is substantially opaque to ambient light.
39. the system according to any claim in claim 31 to 38, it includes self contained pocket power supplys, are used for
It is supplied electric power to the detector and the excitation light source, is pocket thus without external power supply and the system.
40. system according to claim 39, wherein the power supply includes battery.
41. the system according to any claim in claim 31 to 36, wherein the system is comprised in shell,
The shell is defined no more than 750cm3Volume.
42. the system according to any claim in claim 37 to 40, wherein the shell is defined no more than 750cm3
Volume.
43. the system according to any claim in claim 31 to 42, wherein the total weight of the system is no more than
2lbs。
44. the system according to any claim in claim 31 to 43, wherein the polymer optical fiber doped with by
Body dye composite, and the operable donor particle in the inside for being intended to be introduced into the polymer optical fiber of the excitation light source
Including donor dye composition excitation wavelength under irradiate the polymer optical fiber.
45. system according to claim 44, wherein the detector to the polymer optical fiber adulterated described in by
The light of the launch wavelength of body dye composite reacts.
46. system according to claim 45, it includes be positioned between the polymer optical fiber and the detector
Optical filter, wherein the optical filter corresponds to wavelength the light of the excitation wavelength of the donor dye composition substantially not
The transparent and described optical filter substantially transmission peak wavelength corresponds to the acceptor dye combination that the polymer optical fiber is adulterated
The light of the launch wavelength of object.
47. the system according to any claim in claim 31 to 43, wherein the polymer optical fiber is doped with confession
Body dye composite, and the excitation light source is operable with described in the irradiation under the excitation wavelength of the donor dye composition
Polymer optical fiber.
48. system according to claim 47, wherein in inside of the detector to being intended to be introduced into the polymer optical fiber
The light of launch wavelength of the acceptor particles acceptor dye composition that is included react.
49. system according to claim 48, it includes be positioned between the polymer optical fiber and the detector
Optical filter, wherein the optical filter corresponds to wavelength the institute for the donor dye composition that the polymer optical fiber is adulterated
The light for stating excitation wavelength is substantially opaque and the optical filter substantially transmission peak wavelength is combined corresponding to the acceptor dye
The light of the launch wavelength of object.
50. the system according to any claim in claim 31 to 43, it includes polymer optical fiber beam, the optical fiber
Each polymer optical fiber of beam is doped with corresponding acceptor dye composition and/or donor dye composition.
51. system according to claim 50, wherein multiple polymer optical fibers of the fiber optic bundle respectively have different knots
It closes collocation object and is coupled to its inner surface.
52. system according to claim 50, wherein：
The first polymer optical fiber of the fiber optic bundle doped with the first acceptor dye composition with the first launch wavelength,
The second polymer optical fiber of the fiber optic bundle is described doped with the Co receptor dye composite with the second launch wavelength
Second launch wavelength is different from first launch wavelength,
The first polymer optical fiber of the fiber optic bundle has first object of arranging in pairs or groups is combined to be coupled to its inner surface, and
The second polymer optical fiber of the fiber optic bundle has second object of arranging in pairs or groups is combined to be coupled to its inner surface, second knot
It closes collocation object and is different from the first combination collocation object.
53. system according to claim 52, it includes the first detector and the second detector, first detector pair
First launch wavelength reacts and second detector reacts to second launch wavelength.
54. the system according to any claim in claim 52 or 53, it includes the first optical filters and second to filter
Piece, wherein
First optical filter substantially transmits first launch wavelength and substantially impermeable to second launch wavelength
It is bright, and
Second optical filter substantially transmits second launch wavelength and substantially impermeable to first launch wavelength
It is bright.
55. system according to claim 50, wherein：
The first polymer optical fiber of the fiber optic bundle doped with the first donor dye composition with the first excitation wavelength,
The second polymer optical fiber of the fiber optic bundle is described doped with the second donor dye composition with the second excitation wavelength
Second excitation wavelength is different from first excitation wavelength,
The first polymer optical fiber of the fiber optic bundle has first object of arranging in pairs or groups is combined to be coupled to its inner surface, and
The second polymer optical fiber of the fiber optic bundle has second object of arranging in pairs or groups is combined to be coupled to its inner surface, second knot
It closes collocation object and is different from the first combination collocation object.
56. system according to claim 55, it includes the first excitaton source and the second excitaton source, first excitaton source can
Operation under first excitation wavelength to irradiate the fiber optic bundle and second excitaton source is operable with described second
The fiber optic bundle is irradiated under launch wavelength.
57. the system according to any claim in claim 50 or 51, wherein the detector is to include multiple pictures
The focal plane arrays (FPA) of element, and emit light and irradiate the focal plane array out of each polymer optical fiber of the polymer optical fiber beam
The different pixels group of row.
58. a kind of for detecting the signal from hollow core polymer optical fiber to carry out single analyte and/or multiple analytes
The pocket system of detection, the system include：
Detector；
For keeping polymer optical fiber and/or polymer optical fiber beam and it being made to be installed with the optical fiber of the detector in line
Frame；
Excitaton source for irradiating the polymer optical fiber and/or the polymer optical fiber beam with exciting light；And
Shell, wherein：
The shell surrounds the detector, the optical fiber mounting bracket and the excitaton source, and
The shell is substantially opaque to ambient light.
59. system according to claim 58, wherein the detector leaves the polymer light by alignment to detect
The light of fine end face.
60. the system according to any claim in claim 58 or 59, wherein the detector by being aligned so that
It obtains its zone of action and the axis of the polymer optical fiber is substantially concentric.
61. the system according to any claim in claim 58 to 60, wherein the excitation light source by alignment with
Length along the polymer optical fiber irradiates the polymer optical fiber.
62. the system according to any claim in claim 58 to 60, wherein the excitation light source by alignment with
The polymer optical fiber is being irradiated on the direction of the polymer optical fiber.
63. the system according to any claim in claim 58 to 62, wherein the excitation light source is with substantially
The laser of single wavelength operation.
64. the system according to any claim in claim 58 to 63, wherein the shell is defined no more than 750cm3
Volume.
65. the system according to any claim in claim 58 to 64, wherein the total weight of the system is no more than
2lbs。
66. the system according to any claim in claim 58 to 65, wherein the detector is to acceptor dye group
The launch wavelength for closing object reacts so that detector detection is from polymer optical fiber and/or doped with the acceptor dye
The transmitting light of the acceptor particles of composition.
67. the system according to any claim in claim 58 to 66, it includes be positioned in front of the detector
Optical filter, wherein the optical filter is substantially opaque to the light of the wavelength with the exciting light, and the optical filter
Substantially transmission peak wavelength corresponds to the light of the launch wavelength of acceptor dye composition, and the filter transmission is thus made to carry out auto polymerization
The transmitting light of object light fibre and/or the acceptor particles doped with the acceptor dye composition.
68. the system according to any claim in claim 58 to 67, it includes the first detectors and second to detect
First launch wavelength of device, the first acceptor dye of the first detector pair composition reacts, and second detector
It reacts to the second launch wavelength of Co receptor dye composite, is sent out wherein second launch wavelength is different from described first
Ejected wave is long.
69. the system according to any claim in claim 58 to 68, it includes the first optical filters and second to filter
Piece, wherein
First optical filter substantially transmits the first launch wavelength of the first acceptor dye composition and contaminates Co receptor
Second launch wavelength of feed composition is substantially opaque, wherein second launch wavelength is different from first transmitted wave
It is long, and
Second optical filter substantially transmits second launch wavelength and substantially impermeable to first launch wavelength
It is bright.
70. the system according to any claim in claim 58 to 69, it includes the first excitaton sources and second to excite
Source, first excitaton source are operable to generate first excitation wavelength with the excitation wavelength corresponding to donor dye composition
Exciting light, and second excitaton source it is operable with generate have corresponding to the second donor dye composition excitation wavelength
The second excitation wavelength exciting light, wherein second excitation wavelength be different from first excitation wavelength.
71. a kind of method for detecting and/or quantifying one or more analyte of interest in sample, the method include：
Sample solution is introduced into the inside of polymer optical fiber, the solution includes one or more described analyte of interest and confession
Body particle, the donor particle includes that donor dye composition and particle combine collocation object, wherein the polymer optical fiber includes
Acceptor dye composition and optical fiber combine collocation object；
Exciting light is conducted through the polymer optical fiber；And
Detection travels across the transmitting light of the polymer optical fiber, and the transmitting is just generated by singlet oxygen channel, thus
The analyte of interest in detection and/or the quantitative sample.
72. method according to claim 71, it includes multiple polymer that sample solution is introduced to polymer optical fiber beam
In the inside of optical fiber, wherein each polymer optical fiber is doped with corresponding acceptor dye composition and includes that corresponding optical fiber combines collocation
Object.
73. according to the method described in claim 72, do not share the same light wherein multiple polymer optical fibers of the fiber optic bundle respectively have
Fibre combines collocation object to be coupled to its inner surface.
74. according to the method described in claim 73, wherein：
The first polymer optical fiber of the fiber optic bundle doped with the first acceptor dye composition with the first launch wavelength,
The second polymer optical fiber of the fiber optic bundle is described doped with the Co receptor dye composite with the second launch wavelength
Second launch wavelength is different from first launch wavelength,
There is the first polymer optical fiber of the fiber optic bundle the first optical fiber collocation object to be combined to be coupled to its inner surface, and
There is the second polymer optical fiber of the fiber optic bundle the second optical fiber collocation object to be combined to be coupled to its inner surface, and described the
Two optical fiber are different from first optical fiber in conjunction with collocation object and combine collocation object.
75. method according to claim 74, it includes diacritically Detection wavelengths to correspond to first launch wavelength
Light and wavelength correspond to second launch wavelength light.
76. the method according to any claim in claim 74 or 75, it includes：
It will be introduced into the sample solution in conjunction with the first donor particle of collocation object comprising donor dye composition and the first particle,
Wherein described first particle combines collocation object to be bound to the first analyte, and first optical fiber is in conjunction with collocation object also in relation with described in
First analyte；
It will be introduced into the sample solution in conjunction with the second donor particle of collocation object comprising donor dye composition and the second particle,
Wherein described second particle combines collocation object to be bound to the second analyte, and second optical fiber is in conjunction with collocation object also in relation with described in
Second analyte；
The polymer optical fiber will be introduced comprising the sample solution of the first donor particle and the second donor particle
In the inside of the polymer optical fiber of beam.
77. the method according to any claim in claim 72 to 76, it includes：
(a) sample will be introduced in conjunction with the first donor particle of collocation object comprising the first donor dye composition and the first particle
In solution, wherein first particle combines collocation object to be bound to the first analyte；
(b) sample will be introduced in conjunction with the second donor particle of collocation object comprising the second donor dye composition and the second particle
In solution, wherein second particle combines collocation object to be bound to the second analyte；
(c) sample solution comprising the first donor particle and the second donor particle is introduced into the fiber optic bundle
In the inside of the polymer optical fiber, wherein：
There is the first polymer optical fiber of the fiber optic bundle the first optical fiber collocation object to be combined to be coupled to its inner surface,
There is the second polymer optical fiber of the fiber optic bundle the second optical fiber collocation object to be combined to be coupled to its inner surface, second knot
It closes collocation object and is different from the first combination collocation object,
First optical fiber is bound to first analyte in conjunction with collocation object, and
Second optical fiber is bound to second analyte in conjunction with collocation object；
(d) it irradiates the fiber optic bundle with the exciting light with first wave length and detects thus obtained transmitting light, the first wave
The long excitation wavelength corresponding to the first donor dye composition；And
(e) it irradiates the fiber optic bundle with the exciting light with second wave length and detects thus obtained transmitting light, second wave
The long excitation wavelength corresponding to the second donor dye composition.
78. a kind of method for detecting and/or quantifying one or more analyte of interest in sample, the method include：
Sample solution is introduced into the inside of polymer optical fiber, the solution includes one or more analyte of interest and receptor grain
Son, the acceptor particles include that acceptor dye composition and particle combine collocation object, wherein the polymer optical fiber includes donor
Dye composite and optical fiber combine collocation object；
Exciting light is conducted through the polymer optical fiber；And
Detection travels across the transmitting light of the polymer optical fiber, and the transmitting is just generated by singlet oxygen channel, thus
The analyte of interest in detection and/or the quantitative sample.
79. according to the method described in claim 78, it includes multiple polymer that sample solution is introduced to polymer optical fiber beam
In the inside of optical fiber, wherein each polymer optical fiber is doped with corresponding donor dye composition and includes that corresponding optical fiber combines collocation
Object.
80. according to the method described in claim 79, wherein multiple polymer optical fibers of the polymer optical fiber beam respectively have
Different optical fiber combine collocation object to be coupled to its inner surface.
81. the method according to any claim in claim 79 or 80, it includes：
It is molten by the sample is introduced in conjunction with the first acceptor particles of collocation object comprising the first acceptor dye composition and the first particle
In liquid, wherein the first acceptor dye composition has the first launch wavelength；
It is molten by the sample is introduced in conjunction with the Co receptor particle of collocation object comprising Co receptor dye composite and the second particle
In liquid, wherein there is the Co receptor dye composite the second launch wavelength, second launch wavelength to be different from described the
One launch wavelength, and second particle is different from first particle in conjunction with collocation object and combines collocation object；
The sample solution comprising first acceptor particles and the Co receptor particle is introduced to the institute of the fiber optic bundle
In the inside for stating polymer optical fiber, wherein：
There is one or more polymer optical fibers of the fiber optic bundle the first optical fiber collocation object to be combined to be coupled to inner surface, wherein described
First optical fiber combines collocation object to be bound to the first analyte, and first particle is analyzed in conjunction with collocation object also in relation with extremely described first
Object, and
There is one or more polymer optical fibers of the fiber optic bundle the second optical fiber collocation object to be combined to be coupled to inner surface, wherein described
Second optical fiber combines collocation object to be bound to the second analyte, and second particle is analyzed in conjunction with collocation object also in relation with extremely described second
Object.
82. according to the method described in claim 81, it includes diacritically Detection wavelengths to correspond to first launch wavelength
Light and wavelength correspond to second launch wavelength light.
83. the method according to any claim in claim 79 to 82, it includes：
(a) the first acceptor particles comprising the first particle in conjunction with collocation object are introduced into the sample solution, wherein described first
Particle combines collocation object to be bound to the first analyte；
(b) the Co receptor particle comprising the second particle in conjunction with collocation object is introduced into the sample solution, wherein described second
Particle combines collocation object to be bound to the second analyte；
(c) sample solution comprising first acceptor particles and the Co receptor particle is introduced into the fiber optic bundle
In the inside of the polymer optical fiber, wherein：
The first polymer optical fiber of the fiber optic bundle is taken doped with the first donor dye composition and with the combination of the first optical fiber
It is coupled to its inner surface with object,
The second polymer optical fiber of the fiber optic bundle is taken doped with the second donor dye composition and with the combination of the second optical fiber
It is coupled to its inner surface with object, described second is different from described first in conjunction with collocation object combines collocation object,
First optical fiber is bound to first analyte in conjunction with collocation object,
Second optical fiber is bound to second analyte in conjunction with collocation object；
(d) it irradiates the fiber optic bundle with the exciting light with first wave length and detects thus obtained transmitting light, the first wave
The long excitation wavelength corresponding to the first donor dye composition；And
(e) it irradiates the fiber optic bundle with the exciting light with second wave length and detects thus obtained transmitting light, second wave
The long excitation wavelength corresponding to the second donor dye composition.
84. the method according to any claim in claim 71 or 78, wherein by described in sample solution introducing
It, will from there through capillarity comprising the polymer optical fiber is immersed in the sample solution in the inside of polymer optical fiber
The sample solution sucks in the inside of the polymer optical fiber.
85. the method according to any claim in claim 71 or 78, wherein the particle combines collocation object at least
The first analyte being bound in one or more described analyte of interest and the optical fiber combine collocation object also in relation with to institute
State the first analyte.
86. the method according to any claim in claim 71 or 78, wherein the polymer optical fiber is along its length
Including multiple discontinuous parts, respectively the first or second with various concentration combines collocation object to be coupled to for the part
Its inner surface is to realize the measurement to a variety of level of sensitivity of the analyte of interest.
87. the method according to any claim in claim 71 or 78, wherein the polymer optical fiber is along its length
Including multiple discontinuous parts, respectively there is different combinations collocation object to be coupled to its inner surface for the part.
88. a kind of kit, it includes：
Polymer optical fiber according to any claim in claim 1 to 23；And
It is used to prepare one or more reagents of the sample for detecting one or more analyte of interest, one or more described reagents
Including acceptor particles and/or donor particle.
89. a kind of kit, it includes：
Polymer optical fiber beam according to any claim in claim 24 to 28；And
It is used to prepare one or more reagents of the sample for detecting one or more analyte of interest, one or more described reagents
Including acceptor particles and/or donor particle.
90. a kind of kit, it includes：
Chuck according to any claim in claim 29 or 30；And
It is used to prepare one or more reagents of the sample for detecting one or more analyte of interest, one or more described reagents
Including acceptor particles and/or donor particle.
91. a kind of manufacture includes doped with the method for the polymer optical fiber of acceptor dye composition, the method：
The inner surface of the polymer optical fiber is set to be contacted with chemiluminescence singlet oxygen receptor and following at least one：(i) glimmering
Optical compounds and (ii) quantum dot.
92. a method of the polymer optical fiber doped with donor dye composition being manufactured, the method includes：
Make the inner surface and photosensitising agent of the polymer optical fiber.
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| US62/259,000 | 2015-11-23 | ||
| PCT/US2016/063400 WO2017091609A1 (en) | 2015-11-23 | 2016-11-22 | Hollow polymer fiber optic system for single analyte and multiplexed analyte detection |
Publications (2)
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| CN108351303A true CN108351303A (en) | 2018-07-31 |
| CN108351303B CN108351303B (en) | 2022-05-17 |
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| CN201680066530.3A Active CN108351303B (en) | 2015-11-23 | 2016-11-22 | Hollow polymer fiber optic system for single analyte and multiplexed analyte detection |
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| US (3) | US10677735B2 (en) |
| EP (1) | EP3380827B1 (en) |
| CN (1) | CN108351303B (en) |
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Also Published As
| Publication number | Publication date |
|---|---|
| AU2021209272B2 (en) | 2022-11-24 |
| AU2016361420A1 (en) | 2018-04-19 |
| AU2016361420B2 (en) | 2021-05-06 |
| AU2021209272A1 (en) | 2021-08-19 |
| US20210172942A1 (en) | 2021-06-10 |
| US10677735B2 (en) | 2020-06-09 |
| EP3380827A1 (en) | 2018-10-03 |
| WO2017091609A1 (en) | 2017-06-01 |
| US10942177B2 (en) | 2021-03-09 |
| US20170167984A1 (en) | 2017-06-15 |
| US20200232926A1 (en) | 2020-07-23 |
| CN108351303B (en) | 2022-05-17 |
| CA3001020A1 (en) | 2017-06-01 |
| EP3380827B1 (en) | 2023-11-29 |
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